condition_query_response.md

{ "studies": [ { "protocolSection": { "identificationModule": { "nctId": "NCT05288205", "orgStudyIdInfo": { "id": "JAB-21822-1006" }, "organization": { "fullName": "Allist Pharmaceuticals, Inc.", "class": "INDUSTRY" }, "briefTitle": "Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation", "officialTitle": "A Phase 1/2a Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Antitumor Activity of JAB-21822 in Combination With JAB-3312 in Patients With Advanced Solid Tumors Harboring KRAS p.G12C Mutation" }, "statusModule": { "statusVerifiedDate": "2025-03", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2022-04-14", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2026-03", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2026-03", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2022-03-11", "studyFirstSubmitQcDate": "2022-03-11", "studyFirstPostDateStruct": { "date": "2022-03-21", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-04-03", "lastUpdatePostDateStruct": { "date": "2025-04-04", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Allist Pharmaceuticals, Inc.", "class": "INDUSTRY" } }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false, "isUsExport": false }, "descriptionModule": { "briefSummary": "This is a multicenter, open-label phase 1/2a study consisting of two parts: dose escalation phase and dose expansion phase. The objective of the dose escalation phase is to evaluate the safety, tolerability and pharmacokinetics of JAB-21822 in combination with JAB-3312 in patients with advanced solid tumors harboring KRAS p.G12C mutation and to determine the RP2D for the combination therapy. In the dose expansion phase, preliminary efficacy and safety of the combination therapy at the RP2D will be further explored in patients with specific cancer harboring KRAS p.G12C mutation." }, "conditionsModule": { "conditions": [ "KRAS P.G12C", "Non-small Cell Lung Cancer", "Colorectal Cancer", "Pancreatic Ductal Carcinoma" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "NON_RANDOMIZED", "interventionModel": "SEQUENTIAL", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 240, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Dose escalation", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: JAB-21822", "Drug: JAB-3312" ] }, { "label": "Dose expansion", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: JAB-21822", "Drug: JAB-3312" ] } ], "interventions": [ { "type": "DRUG", "name": "JAB-21822", "description": "KRAS G12C inhibitor", "armGroupLabels": [ "Dose escalation", "Dose expansion" ] }, { "type": "DRUG", "name": "JAB-3312", "description": "SHP2 inhibitor", "armGroupLabels": [ "Dose escalation", "Dose expansion" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "recommended phase-2 dose (RP2D).", "description": "RP2D should be selected based on a comprehensive assessment of maximum tolerated dose(MTD), toxicity, pharmacokinetic(PK) profile, and efficacy data.", "timeFrame": "Approximately 2 years" }, { "measure": "Number of participants with dose limiting toxicities", "description": "Dose-limiting toxicity (DLT) is defined as an adverse event (AE) or clinically significant abnormal laboratory value occurring in Cycle 1 (DLT assessment period), which is unrelated to progressive disease, concurrent disease, or concomitant medication but related to JAB-21822 and/or JAB-3312, and meets the criteria for DLT.", "timeFrame": "Approximately 2 years" } ], "secondaryOutcomes": [ { "measure": "Number of participants with AEs", "description": "All patients participating in this study will be assessed for incidence and severity of AEs and serious AEs, including changes in laboratory values, vital signs, electrocardiograms, cardiac imagings and ophthalmological assessments", "timeFrame": "Approximately 2 years" }, { "measure": "Objective response rate (ORR)", "description": "ORR is defined as the proportion of participants with confirmed complete response or partial response", "timeFrame": "Approximately 2 years" }, { "measure": "Progression-free survival (PFS)", "description": "Period of time from the start of treatment to tumor progression or death from any cause (whichever occurs first) based on RECIST v1.1", "timeFrame": "Approximately 2 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* A written informed consent should be signed by a subject or his/her legal representative before any study-related procedures are performed;\n* Subjects with histologically or cytologically confirmed locally advanced or metastatic advanced solid tumors harboring KRAS p.G12C mutation who have failed or lack standard-of-care (SOC) or are unwilling to undergo or intolerant to SOC;\n* Expected survival ≥ 3 months;\n* Subjects must have at least one measurable lesion as defined by RECIST v1.1. If no measurable lesion untreated with radiation is selected as the target lesion, a lesion treated with radiation ≥ 4 weeks before the first dose and with progression confirmed by radiography may be selected as the target lesion;\n* Eastern Cooperative Oncology Group(ECOG) performance status 0-1;\n* The organ functions of subjects meet the criteria for the following laboratory parameters at screening;\n* Subjects must be able to swallow oral medications without gastrointestinal abnormalities that significantly affect drug absorption\n\nExclusion Criteria:\n\n* Patients with previous (≤ 3 years) or current tumors of other pathological types, except for cured cervical carcinoma in situ, ductal carcinoma in situ of the breast, prostatic intraepithelial neoplasia, superficial non-invasive bladder cancer, stage I skin cancer (except melanoma); subjects without recurrence or metastasis for \> 3 years after treatment, without current evidence of tumor, and without significant risk of recurrence of previous malignant diseases in the opinion of the study doctor may also be enrolled;\n* Serious allergy to the investigational drug or excipients (such as microcrystalline cellulose, etc.);\n* Patients with previous (≤ 6 months before the initiation of treatment) or current severe autoimmune diseases (including adverse reactions caused by previous anti- tumor immunotherapies), or autoimmune diseases requiring long-term systemic hormone therapy at immunosuppressive dose levels (prednisone \> 10 mg/day or equivalent drugs);\n* HIV, hepatitis B virus(HBV), or hepatitis C virus(HCV) positive;\n* Previous (≤ 6 months prior to the first dose) or current evidence of the following diseases: acute myocardial infarction, unstable angina and cerebrovascular accident;\n* Subjects who have impaired cardiac functions or clinically significant cardiac diseases;\n* Pregnant or lactating women", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Shanghai Allist Pharmaceuticals Co., Ltd Shanghai Allist Pharmaceuticals Co., Ltd", "role": "CONTACT", "phone": "021-80423288", "email": "zhenhua.gong@allist.com.cn" } ], "overallOfficials": [ { "name": "Wang Wang Jie M.D.", "affiliation": "Peking University Cancer Hospital & Institute", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "The First Affiliated Hospital of USTC Anhui Provincial Hospital", "status": "NOT_YET_RECRUITING", "city": "Hefei", "state": "Anhui", "zip": "230001", "country": "China", "geoPoint": { "lat": 31.86389, "lon": 117.28083 } }, { "facility": "Pecking Union Medical College Hospital", "status": "NOT_YET_RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100005", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Cancer Hospital Chinese Academy Of Medical Sciences", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100021", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Beijing Tiantan Hospital, Captal Medical University", "status": "NOT_YET_RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100070", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Beijing Cancer Hospital", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100142", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Peking University Third Hospital", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100191", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Beijing Chest Hospital, Capital Medical University", "status": "NOT_YET_RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "101125", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Fujian cancer Hospital", "status": "NOT_YET_RECRUITING", "city": "Fuzhou", "state": "Fujian", "zip": "350014", "country": "China", "geoPoint": { "lat": 26.06139, "lon": 119.30611 } }, { "facility": "The First Affiliated Hospital Xiamen University", "status": "NOT_YET_RECRUITING", "city": "Xiamen", "state": "Fujian", "zip": "361003", "country": "China", "geoPoint": { "lat": 24.47979, "lon": 118.08187 } }, { "facility": "The first Affiliated Hospital, Sun Yat-sen University", "status": "NOT_YET_RECRUITING", "city": "Guangzhou", "state": "Guangdong", "zip": "510080", "country": "China", "geoPoint": { "lat": 23.11667, "lon": 113.25 } }, { "facility": "Zhujiang Hospital of Southem Medical University", "status": "NOT_YET_RECRUITING", "city": "Guangzhou", "state": "Guangdong", "zip": "510280", "country": "China", "geoPoint": { "lat": 23.11667, "lon": 113.25 } }, { "facility": "Cancer Hospital Chinese Academy Of medical Sciences Shenzhen Center", "status": "NOT_YET_RECRUITING", "city": "Shenzhen", "state": "Guangdong", "zip": "518116", "country": "China", "geoPoint": { "lat": 22.54554, "lon": 114.0683 } }, { "facility": "Harbin Medical University Cancer Hospital-Mammary gland of internal", "status": "NOT_YET_RECRUITING", "city": "Harbin", "state": "Heilongjiang", "zip": "150081", "country": "China", "geoPoint": { "lat": 45.75, "lon": 126.65 } }, { "facility": "Henan Cancer Hospital", "status": "NOT_YET_RECRUITING", "city": "Zhengzhou", "state": "Henan", "zip": "450003", "country": "China", "geoPoint": { "lat": 34.75778, "lon": 113.64861 } }, { "facility": "The First Affiliated Hosipital Of Zhengzhou University", "status": "NOT_YET_RECRUITING", "city": "Zhengzhou", "state": "Henan", "zip": "450052", "country": "China", "geoPoint": { "lat": 34.75778, "lon": 113.64861 } }, { "facility": "Union Hospital Tongji Medical College Huazhong University of Science and Technology", "status": "NOT_YET_RECRUITING", "city": "Wuhan", "state": "Hubei", "zip": "430022", "country": "China", "geoPoint": { "lat": 30.58333, "lon": 114.26667 } }, { "facility": "Tongji Hospital Tongji Medical College of Hust", "status": "NOT_YET_RECRUITING", "city": "Wuhan", "state": "Hubei", "zip": "430030", "country": "China", "geoPoint": { "lat": 30.58333, "lon": 114.26667 } }, { "facility": "Renmin Hospital Of Wuhan University", "status": "NOT_YET_RECRUITING", "city": "Wuhan", "state": "Hubei", "zip": "430060", "country": "China", "geoPoint": { "lat": 30.58333, "lon": 114.26667 } }, { "facility": "Xiangya Hospital Central South Univesity", "status": "NOT_YET_RECRUITING", "city": "Changsha", "state": "Hunan", "zip": "410008", "country": "China", "geoPoint": { "lat": 28.19874, "lon": 112.97087 } }, { "facility": "Hunan Cancer Hospital", "status": "NOT_YET_RECRUITING", "city": "Changsha", "state": "Hunan", "zip": "410031", "country": "China", "geoPoint": { "lat": 28.19874, "lon": 112.97087 } }, { "facility": "The First Hospital Of China Medical University", "status": "NOT_YET_RECRUITING", "city": "Shenyang", "state": "Liaoning", "zip": "110001", "country": "China", "geoPoint": { "lat": 41.79222, "lon": 123.43278 } }, { "facility": "The Affilated Hospital of Inner Mongolia Medical University", "status": "NOT_YET_RECRUITING", "city": "Hohhot", "state": "Neimenggu", "zip": "750306", "country": "China", "geoPoint": { "lat": 40.81056, "lon": 111.65222 } }, { "facility": "Qilu Hospital of Shandong University", "status": "NOT_YET_RECRUITING", "city": "Jinan", "state": "Shandong", "zip": "250012", "country": "China", "geoPoint": { "lat": 36.66833, "lon": 116.99722 } }, { "facility": "Shandong Cancer Hospital", "status": "NOT_YET_RECRUITING", "city": "Jinan", "state": "Shandong", "zip": "250117", "country": "China", "geoPoint": { "lat": 36.66833, "lon": 116.99722 } }, { "facility": "LinYi Cancer Hospital", "status": "NOT_YET_RECRUITING", "city": "Linyi", "state": "Shandong", "zip": "276002", "country": "China", "geoPoint": { "lat": 35.06306, "lon": 118.34278 } }, { "facility": "Fudan University Shanghai Cancer Center", "status": "NOT_YET_RECRUITING", "city": "Shanghai", "state": "Shanghai Municipality", "zip": "200032", "country": "China", "geoPoint": { "lat": 31.22222, "lon": 121.45806 } }, { "facility": "The Second Affiliated Hospital Zhejiang School of Medicine", "status": "NOT_YET_RECRUITING", "city": "Hangzhou", "state": "Zhejiang", "zip": "310009", "country": "China", "geoPoint": { "lat": 30.29365, "lon": 120.16142 } } ] }, "referencesModule": { "references": [ { "pmid": "40333694", "type": "DERIVED", "citation": "Kang D, Wang Y, Lin Y, Ma WW, Morgensztern D, Leventakos K, Bi C, Ding Y, Xiong J, Yan M, Sun X, Wang P, Ma C, Wang Y. JAB-3312, a Potent Allosteric SHP2 Inhibitor That Enhances the Efficacy of RTK/RAS/MAPK and PD-1 Blockade Therapies. Clin Cancer Res. 2025 Jul 15;31(14):3019-3032. doi: 10.1158/1078-0432.CCR-24-3691." } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D002289", "term": "Carcinoma, Non-Small-Cell Lung" }, { "id": "D015179", "term": "Colorectal Neoplasms" }, { "id": "D021441", "term": "Carcinoma, Pancreatic Ductal" } ], "ancestors": [ { "id": "D002283", "term": "Carcinoma, Bronchogenic" }, { "id": "D001984", "term": "Bronchial Neoplasms" }, { "id": "D008175", "term": "Lung Neoplasms" }, { "id": "D012142", "term": "Respiratory Tract Neoplasms" }, { "id": "D013899", "term": "Thoracic Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D008171", "term": "Lung Diseases" }, { "id": "D012140", "term": "Respiratory Tract Diseases" }, { "id": "D007414", "term": "Intestinal Neoplasms" }, { "id": "D005770", "term": "Gastrointestinal Neoplasms" }, { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D005767", "term": "Gastrointestinal Diseases" }, { "id": "D003108", "term": "Colonic Diseases" }, { "id": "D007410", "term": "Intestinal Diseases" }, { "id": "D012002", "term": "Rectal Diseases" }, { "id": "D044584", "term": "Carcinoma, Ductal" }, { "id": "D000230", "term": "Adenocarcinoma" }, { "id": "D002277", "term": "Carcinoma" }, { "id": "D009375", "term": "Neoplasms, Glandular and Epithelial" }, { "id": "D009370", "term": "Neoplasms by Histologic Type" }, { "id": "D018299", "term": "Neoplasms, Ductal, Lobular, and Medullary" }, { "id": "D010190", "term": "Pancreatic Neoplasms" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT03745326", "orgStudyIdInfo": { "id": "190017" }, "secondaryIdInfos": [ { "id": "19-C-0017" } ], "organization": { "fullName": "National Institutes of Health Clinical Center (CC)", "class": "NIH" }, "briefTitle": "Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A11:01 Patients", "officialTitle": "A Phase I/II Study Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A11:01 Patients" }, "statusModule": { "statusVerifiedDate": "2025-09-22", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2019-05-16", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2027-12-01", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2028-12-01", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2018-11-16", "studyFirstSubmitQcDate": "2018-11-16", "studyFirstPostDateStruct": { "date": "2018-11-19", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-09-23", "lastUpdatePostDateStruct": { "date": "2025-09-24", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "National Cancer Institute (NCI)", "class": "NIH" } }, "oversightModule": { "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "Background:\n\nA new cancer therapy takes white blood cells from a person, grows them in a lab, genetically changes them, then gives them back to the person. Researchers think this may help attack tumors in people with certain cancers. It is called gene transfer using anti-KRAS G12D mTCR cells.\n\nObjective:\n\nTo see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink.\n\nEligibility:\n\nAdults ages 18-72 who have cancer with a molecule on the tumors that can be recognized by the study cells\n\nDesign:\n\nParticipants will be screened with medical history, physical exam, scans, photography, and heart, lung, and lab tests.\n\nAn intravenous (IV) catheter will be placed in a large vein in the chest.\n\nParticipants will have leukapheresis. Blood will be removed through a needle in an arm. A machine will divide the blood and collect white blood cells. The rest of the blood will be returned to the participant through a needle in the other arm.\n\nA few weeks later, participants will have a hospital stay. They will:\n\n* Get 2 chemotherapy medicines by IV over 5 days.\n* Get the changed cells through the catheter. Get up to 9 doses of a medicine to help the cells. They may get a shot to stimulate blood cells.\n* Recover in the hospital for up to 3 weeks. They will provide blood samples.\n\nParticipants will take an antibiotic for at least 6 months.\n\nParticipants will have several follow-up visits over 2 years. They will repeat most of the screening tests and may have leukapheresis.\n\nParticipants blood will be collected for several years.", "detailedDescription": "Background:\n\n* We generated an HLA-A11:01-restricted murine T-cell receptor (mTCR) that specifically recognizes the G12D-mutated variant of KRAS (and other RAS family genes), expressed by many human cancers and constructed a single retroviral vector that contains alpha and beta chains that confer recognition of this antigen when transduced into PBL.\n* In co-cultures with HLA-A11:01+ target cells expressing this mutated oncogene, mTCR transduced T-cells lyse target cells and secrete IFN-gamma with high specificity.\n\nObjectives:\n\n-Primary objectives:\n\n* Phase I: Determine the safety of administering PBL transduced with anti-KRAS G12D mTCR in concert with preparative lymphodepletion and high-dose interleukin-2 (IL-2; aldesleukin).\n* Phase II: Determine if anti-KRAS G12D mTCR-transduced PBL can mediate the regression of tumors harboring the RAS G12D mutation.\n\nEligibility:\n\n* Patients must be/have:\n\n * Age greater than or equal to 18 years and less than or eqaul to 72 years\n * HLA-A\11:01 positive\n * Metastatic or unresectable RAS G12D-expressing cancer which has progressed after standard therapy (if available).\n Patients may not have:\n\n * Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide, or fludarabine.\n\nDesign:\n\n* This is a phase I/II, single center study of PBL transduced with anti-KRAS G12D mTCR in HLA-A\11:01 positive patients with advanced solid tumors expressing G12D mutated RAS.\n PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.\n* Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-KRAS G12D mTCR.\n* All patients will receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine.\n* On Day 0, patients will receive their PBL transduced with the anti-KRAS G12D mTCR and will then begin high-dose aldesleukin.\n* A complete evaluation of lesions will be conducted approximately 6 weeks (plus-minus 2 weeks) after treatment.\n* The study will be conducted using a phase I/II Simon minimax design, with two separate cohorts for the Phase II component: Cohort 2a, patients with RAS G12D pancreatic cancer, and Cohort 2b, patients with RAS G12D non-pancreatic cancer.\n* A total of up to 70 patients may be required; approximately 24 patients in the Phase I portion of the study and 46 (21, plus an allowance of up to 2 non-evaluable per Phase II cohort) patients in the Phase II portion of the study." }, "conditionsModule": { "conditions": [ "Gastrointestinal Cancer", "Pancreatic Cancer", "Gastric Cancer", "Colon Cancer", "Rectal Cancer" ], "keywords": [ "Immunotherapy", "Cell Therapy", "KRAS", "HRAS", "NRAS" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "NON_RANDOMIZED", "interventionModel": "SEQUENTIAL", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 70, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "1/Phase I", "type": "EXPERIMENTAL", "description": "Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-KRAS G12D mTCR PBL + highdose aldesleukin", "interventionNames": [ "Drug: Cyclophosphamide", "Drug: Fludarabine", "Drug: Aldesleukin", "Biological: anti-KRAS G12D mTCR PBL" ] }, { "label": "2/Phase II", "type": "EXPERIMENTAL", "description": "Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-KRAS G12D mTCR PBL + high-dose aldesleukin", "interventionNames": [ "Drug: Cyclophosphamide", "Drug: Fludarabine", "Drug: Aldesleukin", "Biological: anti-KRAS G12D mTCR PBL" ] } ], "interventions": [ { "type": "DRUG", "name": "Cyclophosphamide", "description": "Days -7 and -6: Cyclophosphamide 60 mg/kg/day x 2 days IV in 250 mL D5W infused simultaneously with mesna 15 mg/kg/day over 1 hour x 2 days.", "armGroupLabels": [ "1/Phase I", "2/Phase II" ] }, { "type": "DRUG", "name": "Fludarabine", "description": "Days -7 to -3: Fludarabine 25 mg/m\^2/day IVPB daily over 30 minutes for 5 days.", "armGroupLabels": [ "1/Phase I", "2/Phase II" ] }, { "type": "DRUG", "name": "Aldesleukin", "description": "Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 3 days (maximum 9 doses).", "armGroupLabels": [ "1/Phase I", "2/Phase II" ] }, { "type": "BIOLOGICAL", "name": "anti-KRAS G12D mTCR PBL", "description": "Day 0: Cells will be infused intravenously on the Patient Care Unit over 20-30 minutes (2-4 days after the last dose of fludarabine).", "armGroupLabels": [ "1/Phase I", "2/Phase II" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Response rate", "description": "Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)", "timeFrame": "6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per PI discretion" }, { "measure": "Frequency and severity of treatment-related adverse events", "description": "Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT", "timeFrame": "From time of cell infusion to two weeks after cell infusion" } ] }, "eligibilityModule": { "eligibilityCriteria": "-INCLUSION CRITERIA:\n\n1. Measurable (per RECIST v1.1 criteria), metastatic, or unresectable malignancy expressing G12D mutated KRAS as assessed by one of the following methods: RT-PCR on tumor tissue, tumor DNA sequencing, or any other CLIA-certified laboratory test on\n\n resected tissue. Patients shown to have tumors expressing G12D mutated NRAS and HRAS will also be eligible as these oncogenes share complete amino acid homology with G12D mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope.\n2. Patients must be HLA-A\11:01 positive as confirmed by the NIH Department of Transfusion Medicine.\n3. Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology.\n4. Patients must have:\n\n -previously received standard systemic therapy for their advanced cancer and have been either non-responders or have recurred, specifically:\n * Patients with metastatic colorectal cancer must have had at least two systemic chemotherapy regimens that include 5FU, leucovorin, bevacizumab, oxaliplatin, and irinotecan (or similar agents), or have contraindications to receiving those medications.\n * Patients with pancreatic cancer must have received gemcitabine, 5FU, and oxaliplatin (or similar agents), or have contraindications to receiving those medications.\n * Patients with non-small cell lung cancer (NSCLC) must have had appropriate targeted therapy as indicated by abnormalities in ALK, EGFR, or expression of PDL-1. Other patients must have had platinum-based chemotherapy.\n * Patients with ovarian cancer or prostate cancer must have had approved first-line chemotherapy.\n\n OR\n\n -declined standard treatment.\n5. Patients with 3 or fewer brain metastases that are \< 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with\n\n surgically resected brain metastases are eligible.\n6. Age greater than or equal to 18 years and less than or equal to 72 years.\n7. Clinical performance status of ECOG 0 or 1\n8. Patients must be willing to practice birth control from the time of enrollment on this study and for 12 months after the last dose of combined chemotherapy for women and for four months after treatment for men..\n9. Women of child-bearing potential must be willing to undergo a pregnancy test prior to the start of treatment because of the potentially dangerous effects of the treatment on the fetus.\n\n NOTE: Certain malignancies may secrete hormones that produce false positive pregnancy tests. Serial blood testing (e.g. HCG measurements) and/ or ultrasound may be performed for clarification.\n10. Serology\n\n -Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus may be less responsive to the experimental\n\n treatment and more susceptible to its toxicities.)\n\n -Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative\n11. Hematology\n\n * ANC \> 1000/mm\^3 without the support of filgrastim\n * WBC greater than or equal to 2500/mm\^3\n * Platelet count greater than or equal to 80,000/mm\^3\n * Hemoglobin \> 8.0 g/dL. Subjects may be transfused to reach this cut-off.\n12. Chemistry\n\n * Serum ALT/AST less than or equal to 5.0 x ULN\n * Serum creatinine less than or equal to 1.6 mg/dL\n * Total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert s Syndrome, who must have a total bilirubin \< 3.0 mg/dL.\n13. Patients must have completed any prior systemic therapy at the time of enrollment.\n\n Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to less than or equal to grade 1.\n14. Ability of subject to understand and the willingness to sign a written informed consent document.\n15. Willing to sign a durable power of attorney.\n16. Subjects must be co-enrolled on the protocol 03C0277.\n\nEXCLUSION CRITERIA:\n\n1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.\n2. Concurrent systemic steroid therapy.\n3. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.\n4. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).\n5. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)\n6. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.\n7. History of coronary revascularization or ischemic symptoms.\n8. For select patients with a clinical history prompting cardiac evaluation: last known LVEF less than or equal to 45%.\n\nI. For select patients with a clinical history prompting pulmonary evaluation: known FEV1 less than or equal to 50%.\n\nj. Patients who are receiving any other investigational agents.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "72 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "NCI SB Immunotherapy Recruitment Center", "role": "CONTACT", "phone": "(866) 820-4505", "email": "irc@nih.gov" }, { "name": "James C Yang, M.D.", "role": "CONTACT", "phone": "(240) 760-6223", "email": "jamesyang@mail.nih.gov" } ], "overallOfficials": [ { "name": "James C Yang, M.D.", "affiliation": "National Cancer Institute (NCI)", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "National Institutes of Health Clinical Center", "status": "RECRUITING", "city": "Bethesda", "state": "Maryland", "zip": "20892", "country": "United States", "contacts": [ { "name": "For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center", "role": "CONTACT", "phone": "866-820-4505", "email": "irc@nih.gov" } ], "geoPoint": { "lat": 38.98067, "lon": -77.10026 } } ] }, "referencesModule": { "references": [ { "pmid": "9514698", "type": "BACKGROUND", "citation": "Abrams SI, Khleif SN, Bergmann-Leitner ES, Kantor JA, Chung Y, Hamilton JM, Schlom J. Generation of stable CD4+ and CD8+ T cell lines from patients immunized with ras oncogene-derived peptides reflecting codon 12 mutations. Cell Immunol. 1997 Dec 15;182(2):137-51. doi: 10.1006/cimm.1997.1224." }, { "pmid": "21138872", "type": "BACKGROUND", "citation": "Davis JL, Theoret MR, Zheng Z, Lamers CH, Rosenberg SA, Morgan RA. Development of human anti-murine T-cell receptor antibodies in both responding and nonresponding patients enrolled in TCR gene therapy trials. Clin Cancer Res. 2010 Dec 1;16(23):5852-61. doi: 10.1158/1078-0432.CCR-10-1280." }, { "pmid": "26701267", "type": "BACKGROUND", "citation": "Wang QJ, Yu Z, Griffith K, Hanada K, Restifo NP, Yang JC. Identification of T-cell Receptors Targeting KRAS-Mutated Human Tumors. Cancer Immunol Res. 2016 Mar;4(3):204-14. doi: 10.1158/2326-6066.CIR-15-0188. Epub 2015 Dec 23." } ], "seeAlsoLinks": [ { "label": "NIH Clinical Center Detailed Web Page", "url": "https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2019-C-0017.html" } ] }, "ipdSharingStatementModule": { "ipdSharing": "YES", "description": "All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@All collected IPD will be shared with collaborators under the terms of collaborative agreements.", "infoTypes": [ "STUDY_PROTOCOL", "SAP", "ICF" ], "timeFrame": "Clinical data will be available during the study and indefinitely.", "accessCriteria": "Clinical data will be made available via subscription to BTRIS and with the permission of the study PI." } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D005770", "term": "Gastrointestinal Neoplasms" }, { "id": "D010190", "term": "Pancreatic Neoplasms" }, { "id": "D013274", "term": "Stomach Neoplasms" }, { "id": "D003110", "term": "Colonic Neoplasms" }, { "id": "D012004", "term": "Rectal Neoplasms" } ], "ancestors": [ { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D005767", "term": "Gastrointestinal Diseases" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" }, { "id": "D013272", "term": "Stomach Diseases" }, { "id": "D015179", "term": "Colorectal Neoplasms" }, { "id": "D007414", "term": "Intestinal Neoplasms" }, { "id": "D003108", "term": "Colonic Diseases" }, { "id": "D007410", "term": "Intestinal Diseases" }, { "id": "D012002", "term": "Rectal Diseases" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "D003520", "term": "Cyclophosphamide" }, { "id": "C024352", "term": "fludarabine" }, { "id": "C082598", "term": "aldesleukin" } ], "ancestors": [ { "id": "D010752", "term": "Phosphoramide Mustards" }, { "id": "D009588", "term": "Nitrogen Mustard Compounds" }, { "id": "D009150", "term": "Mustard Compounds" }, { "id": "D006846", "term": "Hydrocarbons, Halogenated" }, { "id": "D006838", "term": "Hydrocarbons" }, { "id": "D009930", "term": "Organic Chemicals" }, { "id": "D063088", "term": "Phosphoramides" }, { "id": "D009943", "term": "Organophosphorus Compounds" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT06385925", "orgStudyIdInfo": { "id": "TSN1611-2023-101" }, "organization": { "fullName": "Tyligand Pharmaceuticals (Suzhou) Limited", "class": "INDUSTRY" }, "briefTitle": "A Study of TSN1611 Treating Patients With Advanced Solid Tumors Harboring KRAS G12D Mutation", "officialTitle": "Phase 1/2 Study of TSN1611 in Subjects With Advanced Solid Tumors Harboring KRAS G12D Mutation" }, "statusModule": { "statusVerifiedDate": "2025-03", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2024-04-29", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2026-10-30", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2027-04-30", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2024-04-18", "studyFirstSubmitQcDate": "2024-04-23", "studyFirstPostDateStruct": { "date": "2024-04-26", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-03-19", "lastUpdatePostDateStruct": { "date": "2025-03-24", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Tyligand Pharmaceuticals (Suzhou) Limited", "class": "INDUSTRY" } }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false, "isUsExport": false }, "descriptionModule": { "briefSummary": "The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part.", "detailedDescription": "Phase 1 Part:\n\nThe phase 1 part will evaluate the prespecified dose levels of TSN1611. Dose escalation will continue until up to the highest planned dose or the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is determined. Dose optimization could be performed as indicated by the emerging data.\n\nPhase 2 Part:\n\nPhase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations." }, "conditionsModule": { "conditions": [ "Malignant Neoplasm" ], "keywords": [ "solid tumor", "KRAS G12D mutation", "pancreatic cancer", "colorectal cancer", "non-small cell lung cancer", "malignant neoplasm" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "NON_RANDOMIZED", "interventionModel": "SEQUENTIAL", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 150, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Phase 1: Dose-finding/evaluation of TSN1611 monotherapy", "type": "EXPERIMENTAL", "description": "The phase 1 part will evaluate the prespecified sequential dose levels of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors to determine the recommended dose of TSN1611 for further investigation.", "interventionNames": [ "Drug: TSN1611" ] }, { "label": "Phase 2: Dose expansion of TSN1611 monotherapy", "type": "EXPERIMENTAL", "description": "Phase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose level in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations.", "interventionNames": [ "Drug: TSN1611" ] } ], "interventions": [ { "type": "DRUG", "name": "TSN1611", "description": "TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.", "armGroupLabels": [ "Phase 1: Dose-finding/evaluation of TSN1611 monotherapy", "Phase 2: Dose expansion of TSN1611 monotherapy" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Dose limiting toxicities (DLTs) in phase 1 part", "description": "To determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose(s) (RP2D\[s\]) of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.", "timeFrame": "21 days" }, { "measure": "Objective response rate (ORR) in phase 2 part", "description": "To evaluate the anti-tumor activity of TSN1611 using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.", "timeFrame": "Up to 3 years" } ], "secondaryOutcomes": [ { "measure": "Adverse events", "description": "To assess the safety profile and tolerability of TSN1611 as monotherapy in subjects with KRAS G12D mutant advanced solid tumors.", "timeFrame": "Up to 3 years" }, { "measure": "Area under the plasma concentration-time curve (AUC)", "description": "To characterize the pharmacokinetic (PK) profile of TSN1611.", "timeFrame": "9 weeks" }, { "measure": "Maximum blood concentrations (Cmax)", "description": "To characterize the PK profile of TSN1611.", "timeFrame": "9 weeks" }, { "measure": "Time to maximum blood concentration (Tmax)", "description": "To characterize the PK profile of TSN1611.", "timeFrame": "9 weeks" }, { "measure": "Duration of response (DOR)", "description": "To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.", "timeFrame": "Up to 3 years" }, { "measure": "Time to response (TTR)", "description": "To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.", "timeFrame": "Up to 3 years" }, { "measure": "Disease control rate (DCR)", "description": "To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.", "timeFrame": "Up to 3 years" }, { "measure": "Progression free survival (PFS)", "description": "To evaluate the anti-tumor activity of TSN1611 using RECIST version 1.1.", "timeFrame": "Up to 3 years" }, { "measure": "Overall survival", "timeFrame": "Up to 3 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Subjects must meet all the following inclusion criteria to be eligible for participation in this study:\n\n The subject fully understands the requirements of the study and voluntarily signs the ICF.\n* At least 18 years of age at the time of informed consent.\n* Life expectancy of 3 months or more.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.\n* Subjects with histologically or cytologically confirmed locally advanced or metastatic solid tumor harboring KRAS G12D mutation; subjects must be refractory or intolerable to standard treatment, or have no standard treatment available, etc.\n* Patients with adequate cardiac, liver, renal function, etc.\n\nExclusion Criteria\n\nSubjects will be excluded if they meet any of the following criteria:\n\n* Leptomeningeal disease or Active central nervous system (CNS) metastases.\n* Prior systemic anti-cancer treatment within 21 days or 5 half-lives (whichever is shorter will be used as the criteria) prior to the first dose of study drug.\n* Radical radiation within 4 weeks prior to the first dose of study drug; palliative radiotherapy within 1 week prior to the first dose of study drug.\n* Any unresolved Grade 2 or higher toxicity from previous anticancer therapy except alopecia.\n* Has participated in a study of investigational agent and received the investigational agent within 21 days or 5 half-lives, if known (whichever is shorter) prior to the first dose of study drug.\n* History of interstitial lung disease (ILD), drug induced IDL, or current active pneumonitis, radiation pneumonitis requiring therapeutic intervention, or uncontrolled other lung disease.\n* Any of the following in the past 6 months: myocardial infarction, unstable angina, symptomatic congestive heart failure, stroke or transient ischemic attack, pulmonary embolism.\n* Prior treatment with KRAS G12D targeted therapy.\n* Has a history or current evidence of any severe condition, concurrent therapy, or laboratory abnormality that might confound the interpretation of the study results, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the investigator.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Tyligand Clinical Trial Info", "role": "CONTACT", "phone": "+86 021-50720081", "email": "clinical_trial@tyligand.com" } ], "overallOfficials": [ { "name": "Cindy Li", "affiliation": "Tyligand Bioscience (Shanghai) Limited", "role": "STUDY_DIRECTOR" } ], "locations": [ { "facility": "MD Anderson Cancer Center", "status": "RECRUITING", "city": "Houston", "state": "Texas", "zip": "77030", "country": "United States", "contacts": [ { "name": "Siqing Fu, MD,PhD", "role": "CONTACT" } ], "geoPoint": { "lat": 29.76328, "lon": -95.36327 } }, { "facility": "NEXT Oncology", "status": "RECRUITING", "city": "San Antonio", "state": "Texas", "zip": "78229", "country": "United States", "contacts": [ { "name": "David Sommerhalder, MD", "role": "CONTACT" } ], "geoPoint": { "lat": 29.42412, "lon": -98.49363 } }, { "facility": "NEXT Virginia", "status": "RECRUITING", "city": "Fairfax", "state": "Virginia", "zip": "22031", "country": "United States", "contacts": [ { "name": "Alexander Spira, MD", "role": "CONTACT" } ], "geoPoint": { "lat": 38.84622, "lon": -77.30637 } }, { "facility": "Beijing Cancer Hospital, Beijing, China", "status": "RECRUITING", "city": "Beijing", "zip": "100142", "country": "China", "contacts": [ { "name": "Lin Shen", "role": "CONTACT" }, { "name": "Lin Shen, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Shanghai Chest Hospital, Shanghai, China", "status": "RECRUITING", "city": "Shanghai", "zip": "200030", "country": "China", "contacts": [ { "name": "Shun Lu", "role": "CONTACT" }, { "name": "Shun Lu, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 31.22222, "lon": 121.45806 } }, { "facility": "Shanghai Zhongshan Hospital, Shanghai, China", "status": "RECRUITING", "city": "Shanghai", "zip": "200032", "country": "China", "contacts": [ { "name": "Tianshu Liu", "role": "CONTACT" }, { "name": "Tianshu Liu, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 31.22222, "lon": 121.45806 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D009369", "term": "Neoplasms" }, { "id": "D010190", "term": "Pancreatic Neoplasms" }, { "id": "D015179", "term": "Colorectal Neoplasms" }, { "id": "D002289", "term": "Carcinoma, Non-Small-Cell Lung" } ], "ancestors": [ { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" }, { "id": "D007414", "term": "Intestinal Neoplasms" }, { "id": "D005770", "term": "Gastrointestinal Neoplasms" }, { "id": "D005767", "term": "Gastrointestinal Diseases" }, { "id": "D003108", "term": "Colonic Diseases" }, { "id": "D007410", "term": "Intestinal Diseases" }, { "id": "D012002", "term": "Rectal Diseases" }, { "id": "D002283", "term": "Carcinoma, Bronchogenic" }, { "id": "D001984", "term": "Bronchial Neoplasms" }, { "id": "D008175", "term": "Lung Neoplasms" }, { "id": "D012142", "term": "Respiratory Tract Neoplasms" }, { "id": "D013899", "term": "Thoracic Neoplasms" }, { "id": "D008171", "term": "Lung Diseases" }, { "id": "D012140", "term": "Respiratory Tract Diseases" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT05052671", "orgStudyIdInfo": { "id": "OU-SCC-ctDNA" }, "organization": { "fullName": "University of Oklahoma", "class": "OTHER" }, "briefTitle": "ctDNA Assay in Patients With Resectable Pancreatic Cancer", "officialTitle": "Application of ctDNA Assay in the Neoadjuvant and Adjuvant Chemotherapy Setting in Patients With Resectable Pancreatic Cancer", "acronym": "OU-SCC-ctDNA" }, "statusModule": { "statusVerifiedDate": "2025-02", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2022-05-25", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2025-12", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2027-12", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2021-09-13", "studyFirstSubmitQcDate": "2021-09-13", "studyFirstPostDateStruct": { "date": "2021-09-22", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-02-21", "lastUpdatePostDateStruct": { "date": "2025-02-24", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "University of Oklahoma", "class": "OTHER" }, "collaborators": [ { "name": "Natera, Inc.", "class": "INDUSTRY" } ] }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "The purpose of this study is to determine the proportion of positive ctDNA -freely circulating tumor DNA fragments found in the blood plasma- in patients with pancreatic cancer and to better understand the relationship between possible ctDNA biomarkers and patient survival. A successful study may provide preliminary evidence that helps improve future patient care through targeted diagnostics, prognosis, and/or treatment.", "detailedDescription": "The objective of this study is to assess the role of serial ctDNA analysis as integrative biomarker in patients with resectable or borderline resectable pancreatic cancer undergoing treatment with curative intent. This is a single arm prospective tissue/blood collection from patients undergoing neoadjuvant treatment and Surgery as well as surveillance, plan to accrue up to 50 patients. Primary objective is to determine the proportion of ctDNA positive in patients with resectable pancreatic cancer and to evaluate the progression free survival (PFS) in subjects with ctDNA positive versus ctDNA negative.\n\nPatients who consent to the study will participate in pre-study exams and tests to find out if they can take part in the study. This includes, but is not limited to, a doctor's visit with medical history and physical evaluation, blood work, pregnancy test for those capable of becoming pregnant, and imaging tests.\n\nThe study itself will include the patient's regular treatment for pancreatic cancer which may include 4 to 6 months of chemotherapy, chemo-radiation, surgery to remove pancreatic cancer, 24 weeks of post operative ctDNA surveillance and follow up for 2 years. Blood will be drawn at regular time points during this study for ctDNA detection. The tumor tissue at diagnosis will be collected to develop a personalized and tumor informed PCR test." }, "conditionsModule": { "conditions": [ "Pancreas Cancer" ] }, "designModule": { "studyType": "OBSERVATIONAL", "patientRegistry": false, "designInfo": { "observationalModel": "CASE_ONLY", "timePerspective": "PROSPECTIVE" }, "bioSpec": { "retention": "SAMPLES_WITH_DNA", "description": "Tumor tissue from core biopsy and blood sample for ctDNA assay." }, "enrollmentInfo": { "count": 50, "type": "ESTIMATED" } }, "outcomesModule": { "primaryOutcomes": [ { "measure": "ctDNA Positivity in Patients with Resectable Pancreatic Cancer", "description": "Determine the proportion of ct DNA positivity in patients with resectable pancreatic cancer.", "timeFrame": "Baseline" }, { "measure": "Progression free survival (PFS)", "description": "Determine PFS in ctDNA positive versus ctDNA negative patients.", "timeFrame": "2 years" } ], "secondaryOutcomes": [ { "measure": "Conversion time from ctDNA negative to positive after surgical resection.", "description": "Median time from positive ctDNA to negative ctDNA in patients with pancreatic cancer undergoing surgical resection and adjuvant chemotherapy", "timeFrame": "2 years" }, { "measure": "Median time for select genes to convert from positive to negative.", "description": "Median time from any positive KRAS, CDKN2A, SMAD4, or TP53 genes to become negative", "timeFrame": "2 years" }, { "measure": "Overall survival (OS) in ctDNA positive versus ctDNA negative.", "description": "Comparison of overall survival rate of ctDNA positive versus ctDNA negative patients.", "timeFrame": "2 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria\n\n1. Newly diagnosed exocrine pancreatic cancer with either pathology or radiology imaging suggestive of adenocarcinoma\n2. Resectable/Borderline Resectable Pancreatic cancer as defined by the NCCN guidelines\n3. ≥ 18 years old at the time of informed consent\n4. ECOG Performance Status 0 or 1\n5. Patients who are candidates for neoadjuvant chemo/chemoradiotherapy or upfront surgery are eligible for the study.\n6. Ability to provide written informed consent and HIPAA authorization\n7. Patients must have a life expectancy of at least 6 months\n\nExclusion Criteria\n\n1. Patients with pancreatic malignant tumor histologically confirmed as neuroendocrine or any other type of malignancies\n2. Positive pregnancy test, pregnant, or breastfeeding\n3. Any clinically significant and/or uncontrolled cardiac-related abnormality that would compromise patient safety or the outcome of the study\n4. Locally advanced or metastatic disease", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "99 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ], "studyPopulation": "Patients age 18 or over with newly diagnosed exocrine pancreatic cancer with pathology confirmed adenocarcinoma.", "samplingMethod": "NON_PROBABILITY_SAMPLE" }, "contactsLocationsModule": { "centralContacts": [ { "name": "Lead Nurse", "role": "CONTACT", "phone": "1-405-271-8777", "email": "SCC-IIT-office@ouhsc.edu" } ], "overallOfficials": [ { "name": "Sagila George", "affiliation": "University of Oklahoma", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "University of Oklahoma", "status": "RECRUITING", "city": "Oklahoma City", "state": "Oklahoma", "zip": "73117", "country": "United States", "contacts": [ { "name": "Lead Nurse", "role": "CONTACT", "phone": "405-271-8777", "email": "SCC-IIT-Office@ouhsc.edu" }, { "name": "Sagila George, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 35.46756, "lon": -97.51643 } }, { "facility": "Stephenson Cancer Center- Tulsa", "status": "NOT_YET_RECRUITING", "city": "Tulsa", "state": "Oklahoma", "zip": "74104", "country": "United States", "contacts": [ { "name": "Lead Nurse", "role": "CONTACT", "email": "SCC-IIT-Office@ouhsc.edu" }, { "name": "Laura K Brett, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 36.15398, "lon": -95.99277 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D010190", "term": "Pancreatic Neoplasms" } ], "ancestors": [ { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT05438667", "orgStudyIdInfo": { "id": "[2022]01-01" }, "organization": { "fullName": "Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University", "class": "OTHER" }, "briefTitle": "TCR-T Cell Therapy on Advanced Solid Tumors", "officialTitle": "A Prospective, One Arm Clinical Study on the Safety, Efficacy and Pharmacokinetics of KRAS Mutant Antigen Specific TCR-T Cells in the Treatment of Advanced Solid Tumors." }, "statusModule": { "statusVerifiedDate": "2025-09", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2023-06-01", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2028-06-30", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2028-06-30", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2022-06-07", "studyFirstSubmitQcDate": "2022-06-24", "studyFirstPostDateStruct": { "date": "2022-06-30", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-09-01", "lastUpdatePostDateStruct": { "date": "2025-09-08", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University", "class": "OTHER" } }, "oversightModule": { "oversightHasDmc": true, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "The primary aim of this study is to evaluate the efficacy of KRAS mutant antigen specific TCR-T cells in the treatment of patients with advanced solid tumors.\n\nThe secondary aim is to evaluate the pharmacokinetic/pharmacodynamic characteristics of TCR-T cell therapy in patients with advanced solid tumors and the survival of TCR-T cells.\n\nThe investigators will evaluate the changes of tumor microenvironment after treatment of advanced solid tumors with KRAS mutant antigen specific TCR-T cells; Evaluating the correlation between cytokines and the occurrence of CRS and neurotoxicity", "detailedDescription": "1.This study is a prospective and single arm clinical study. In this trial, 18 patients with advanced solid tumors with KRAS G12V or G12D mutations and matching HLA-A subtypes are recruited for autologous Tumor-T Cell Receptor (TCR) -Mediated T Cells therapy(TCR-T) therapy.Within 3 - 5 days after pretreatment, subjects will receive a single TCR-T infusion with an infusion dose of about 1 × 10⁹～1 × 10¹⁰. Once every 12 hours within 24 hours after TCR-T cell infusion, recombinant human interleukin-2 will be injected intravenously for 5 days .\n\nAfter 3 months of treatment, the patient's condition was evaluated. If the subject did not occur tumor progression and did not occur adverse events (AEs) of level 3 or higher, a second TCR-T cell reinfusion can be performed based on researcher's judgment (informed consent form needs to be signed again).\n\nThe study will evaluate the safety of TCR-T treatment by observing adverse events after cell therapy; evaluate the effectiveness of TCR-T compared to the results or historical data of the subject's own previous standard treatment regimen;and collect blood before and after cell infusion, measure the number and activity of TCR-T cells, and evaluate the pharmacokinetic (PK) characteristics of TCR-T." }, "conditionsModule": { "conditions": [ "Pancreatic Cancer" ], "keywords": [ "Pancreatic Cancer", "PK/PD", "TCR-T", "Safety", "efficacy" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "EARLY_PHASE1" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 18, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "TCR-T treatment group", "type": "EXPERIMENTAL", "description": "Within 3-5 days after pretreatment, subjects will receive a single TCR-T infusion with an infusion dose of about 1 × 10⁹～1 × 10¹⁰.Once every 12 hours within 24 hours after TCR-T cell infusion, recombinant human interleukin-2 will be injected intravenously for 5 days. After 3 months of treatment, the patient's condition was evaluated. If the subject did not occur tumor progression and did not occur adverse events (AEs) of level 3 or higher, a second TCR-T cell reinfusion can be performed .", "interventionNames": [ "Biological: TCR-T therapy" ] } ], "interventions": [ { "type": "BIOLOGICAL", "name": "TCR-T therapy", "description": "1.Preprocessing strategy：\n\n1. Cyclophosphamide: 300-450mg/m², dissolved in 100ml 0.9% sodium chloride saline, intravenous drip for 60minutes, and 0.4g Mesna injected at 0hour, 4hours and 8 hours after cyclophosphamide,4days and 5 days before TCR-T cell infusion.\n2. Fludarabine: 30mg/m² , dissolved in 100ml 0.9% sodium chloride saline, intravenous drip for 30minutes before 3 to 5days before TCR-T cell infusion.\n\n2.Within 3-5 days after pretreatment, subjects will receive a single TCR-T reinfusion with an infusion dose of about 1 × 10⁹～1 × 10¹⁰.\n\n3.Once every 12 hours within 24 hours after TCR-T cell infusion, recombinant human interleukin-2 (injection unit: 500000 units /m², once every 12 hours, subcutaneous injection) will be injected intravenously for 5 days (10 times in total).\n\n4.After 3 months of treatment, If the subject did not occur tumor progression and did not occur adverse events (AEs) of level 3 or higher, a second TCR-T cell reinfusion can be performed.", "armGroupLabels": [ "TCR-T treatment group" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "objective response rate（ORR）", "description": "The objective response rate is calculated based on the patient population with measurable lesions at baseline, with efficacy determined by comparing tumor burden before and after treatment. According to RECIST 1.1 criteria，Complete Response (CR): Disappearance of all target lesions with no new lesions. Partial Response (PR): ≥30% reduction in the sum of diameters of target lesions. Progressive Disease (PD): ≥20% increase in the sum of diameters of target lesions or appearance of new lesions. Stable Disease (SD): Changes not meeting any of the above thresholds.", "timeFrame": "At 12months after the TCR-T cell infusion" } ], "secondaryOutcomes": [ { "measure": "Peak plasma concentration (Cmax)", "description": "Peak plasma concentration (Cmax) refers to the maximum concentration of TCR-T cells in peripheral blood after the TCR-T cells infusion.", "timeFrame": "1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion" }, { "measure": "Area under the plasma concentration versus time curve (AUC)", "description": "Area under the plasma concentration versus time curve (AUC) is used to access the absorbed TCR-T cells dose into human blood circulation after TCR-T cells injection.", "timeFrame": "1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion" }, { "measure": "Peak time (Tmax)", "description": "Peak time (Tmax) refers to the time when the blood concentration reaches the peak after TCR-T cells injection.", "timeFrame": "1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion" }, { "measure": "Cell number of TCR-T cells in peripheral blood", "description": "Cell numbers of TCR-T cells after the injection of TCR-T cells", "timeFrame": "1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion" }, { "measure": "Peak value of cytokines", "description": "The peak value of cytokines within 1 month after TCR-T cell infusion .", "timeFrame": "1、3、7、14、28days and 2months、3 months、6 months、9 months、12months after the TCR-T cell infusion" }, { "measure": "Adverse events", "description": "The type, incidence and severity of adverse events include abnormal laboratory examination results with clinical significance after treatment, abnormal physical examination and blood examination results, bone marrow examination results, etc. Clinical and laboratory adverse events will be classified according to the National Cancer Institute general terminology standard for adverse events (NCI CTCAE) version 5.0.", "timeFrame": "12months after TCR-T infusion" }, { "measure": "duration of response(DOR)", "description": "DOR is defined as the time from the first confirmed objective response to disease progression or recurrence.", "timeFrame": "12months after TCR-T infusion" }, { "measure": "The overall survival(OS)", "description": "The overall survival period refers to the time of the TCR-T infusion to the death of the patient for any cause.", "timeFrame": "At 12months after the TCR-T cell infusion" }, { "measure": "Progression free survival (PFS)", "description": "Progression free survival refers to the time from TCR-T infusion to the first occurrence of disease or death from any cause.According to RECIST version 1.1, the tumor evaluation of all subjects will be evaluated within 12 months after TCR-T treatment.", "timeFrame": "At 12months after the TCR-T cell infusion" }, { "measure": "Time to progression (TTP)", "description": "Time to progression (TTP) refers to the time from TCR-T infusion to objective tumor progression.According to RECIST version 1.1, the tumor evaluation of all subjects will be evaluated within 12 months after TCR-T treatment.", "timeFrame": "12months after the TCR-T cell infusion" }, { "measure": "Event free survival period", "description": "The event free survival period (until the time of treatment failure) refers to the time from entering the trial to any treatment failure, including disease progression or cessation of treatment for any reason (such as disease progression, toxic reactions, subject willingness, initiation of new treatment without clear progression, or death).According to RECIST version 1.1, the tumor evaluation of all subjects will be evaluated within 12 months after TCR-T treatment.", "timeFrame": "At 12months after the TCR-T cell infusion" }, { "measure": "The disease-free survival period", "description": "The disease-free survival period refers to the time from obtaining disease-free status or reaching complete response until recurrence or death due to acute toxicity of tumors or treatment.", "timeFrame": "At 12months after the TCR-T cell infusion" }, { "measure": "The duration of efficacy", "description": "The duration of efficacy refers to the time from reaching the treatment effectiveness (i.e. CR or PR) standard until the first definite recurrence or progression is achieved.", "timeFrame": "At 12months after the TCR-T cell infusion" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria：\n\n1. Age greater than 18 years old；\n2. Subjects with advanced solid tumors confirmed by histology/cytology who have failed standard treatment, are intolerant to standard treatment, or for whom no standard treatment exists. . Non-small cell lung cancer: Recurrent/metastatic non-small cell lung cancer previously treated with platinum-based chemotherapy and/or immunotherapy and/or anti-angiogenic therapy; ii. Pancreatic cancer: Recurrent/metastatic pancreatic cancer that has failed at least one prior systemic therapy; iii. Colorectal cancer: Recurrent/metastatic colorectal cancer that has failed at least two prior systemic therapies (including oxaliplatin, irinotecan, fluoropyrimidine-based agents, anti-angiogenic drugs, etc.); iiii. Other tumors: Other advanced solid tumors that have failed standard treatment, are intolerant to standard treatment, or for which no standard treatment exists;\n3. Previous tissue pathology or peripheral blood testing confirmed the presence of KRAS G12V or G12D mutations with matching HLA subtypes；\n4. Expected survival duration of more than 3 months；\n5. Eastern Cooperative Oncology Group( ECOG )score ≤2；\n6. All participants voluntarily participate in this study and sign an informed consent. And the subjects have good compliance and can cooperate with investigators follow-up study.\n7. Patients at least have had at least one measurable lesion as defined by RECIST v1.1 criteria；\n8. Female participants can not be pregnant or lactating and their serum or urine human chorionic gonadotropin tests must be negative within 72 hours prior to study enrollment；All subjects must be using a medically accepted means of contraception ( (e.g., oral contraceptives, intrauterine device) during the course of this study and for at least 3 months after completion of study therapy.\n9. Organ function and bone marrow reserve are in good condition, and the following requirements must be met:\n\n1)Absolute neutrophil count≥1.5×10⁹/L, Absolute lymphocyte count ≥0.5×10⁹/L；2)Platelet count≥50×10⁹/L；3)Hemoglobin≥90g/L；4)Bilirubin \< 1.5 times upper limit of normal（Bile duct obstruction due to tumor compression were excluded)；5)Serum creatinine ≤ 1.5 times the upper limit of normal range or creatinine clearance ≥ 60 mL/min.6)Serum alanine aminotransferase or aspartate aminotransferase is \< 2.5 times the upper limit of the normal value (ULN) (if patients with liver metastasis, ≤5 times the ULN).7)Coagulation function normalised：INR≤1.5，PTT\<1.2 times the upper limit of normal（Tumor - related anticoagulant therapy was excluded).\n\nExclusion Criteria:\n\n1. Intracranial metastasis or Patients with moderate or severe hydrothorax need drain placement to relieve symptoms.\n2. Active pulmonary tuberculosis\n3. Human immunodeficiency virus (HIV) positive；\n4. Active Hepatitis B or Hepatitis C infection；\n5. Pregnant women and lactating females；\n6. Previous or concurrent history of other malignant tumors. Exceptions include curatively treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy;\n7. Patients with central nervous metastases；\n8. Serious, uncontrolled comorbidities that may affect protocol compliance or interfere with interpretation of results，or any serious medical condition that may affect the safety of the subjects ;\n9. History of clinically significant respiratory diseases or other respiratory diseases that seriously affect Pulmonary function;\n10. Any active autoimmune disease,any condition requiring steroid hormones or immunosuppressive therapy( including but not limited to systemic lupus erythematosus, sjogren's syndrome, rheumatoid arthritis, psoriasis, multiple sclerosis, inflammatory bowel disease, etc., require \> 10 mg/D of prednisone or equivalent hormone）\n11. A history of organ transplantation；\n12. A history of myocardial infarction and severe arrhythmia within six months；Ineligible also includes uncontrolled hypertension, coronary heart disease, stroke, liver cirrhosis, nephritis and other serious complications;\n13. Those who have a history of psychotropic drug abuse and cannot quit or have a history of psychiatric impairment；\n14. Participants with an allergic constitution, known sensitivity to human serum albumin, cyclophosphamide, fludarabine and interleukin 2;\n15. Those with bleeding or thromboembolic tendency：bleeding symptoms of clinical significance or a clear tendency to bleeding within 2 weeks prior to entering the study. And those with hereditary or acquired bleeding and thrombotic tendencies； serious arterial/venous thromboembolic events occurred in the previous 6 months;\n16. Other severe, acute or chronic medical or mental illnesses that in the investigator's judgement will might be increase the risk associated with the patient's participation in the study or interfere with interpretation of research results.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Meng Zhang, MD", "role": "CONTACT", "phone": "+86 02034071785", "email": "sysmhqkyxkek@mail.sysu.edu.cn" }, { "name": "Zhifen Zeng, MD", "role": "CONTACT", "phone": "+86 02034071785", "email": "sysmhqkyxkek@mail.sysu.edu.cn" } ], "overallOfficials": [ { "name": "Meng Zhang, MD", "affiliation": "Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University", "role": "STUDY_CHAIR" } ], "locations": [ { "facility": "Sun Yat-sen Memorial Hospital", "status": "RECRUITING", "city": "Guangzhou", "state": "Guangdong", "zip": "510000", "country": "China", "contacts": [ { "name": "Meng zhang, MD", "role": "CONTACT", "phone": "+86 02034071785", "email": "sysmhqkyxkek@mail.sysu.edu.cn" } ], "geoPoint": { "lat": 23.11667, "lon": 113.25 } } ] }, "referencesModule": { "references": [ { "pmid": "35648703", "type": "BACKGROUND", "citation": "Leidner R, Sanjuan Silva N, Huang H, Sprott D, Zheng C, Shih YP, Leung A, Payne R, Sutcliffe K, Cramer J, Rosenberg SA, Fox BA, Urba WJ, Tran E. Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer. N Engl J Med. 2022 Jun 2;386(22):2112-2119. doi: 10.1056/NEJMoa2119662." }, { "pmid": "27959684", "type": "BACKGROUND", "citation": "Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016 Dec 8;375(23):2255-2262. doi: 10.1056/NEJMoa1609279." }, { "pmid": "26516200", "type": "BACKGROUND", "citation": "Tran E, Ahmadzadeh M, Lu YC, Gros A, Turcotte S, Robbins PF, Gartner JJ, Zheng Z, Li YF, Ray S, Wunderlich JR, Somerville RP, Rosenberg SA. Immunogenicity of somatic mutations in human gastrointestinal cancers. Science. 2015 Dec 11;350(6266):1387-90. doi: 10.1126/science.aad1253. Epub 2015 Oct 29." }, { "pmid": "24812403", "type": "BACKGROUND", "citation": "Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102." }, { "pmid": "16946036", "type": "BACKGROUND", "citation": "Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, Royal RE, Topalian SL, Kammula US, Restifo NP, Zheng Z, Nahvi A, de Vries CR, Rogers-Freezer LJ, Mavroukakis SA, Rosenberg SA. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006 Oct 6;314(5796):126-9. doi: 10.1126/science.1129003. Epub 2006 Aug 31." }, { "pmid": "26299805", "type": "BACKGROUND", "citation": "Morkel M, Riemer P, Blaker H, Sers C. Similar but different: distinct roles for KRAS and BRAF oncogenes in colorectal cancer development and therapy resistance. Oncotarget. 2015 Aug 28;6(25):20785-800. doi: 10.18632/oncotarget.4750." }, { "pmid": "26808342", "type": "BACKGROUND", "citation": "Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J. Cancer statistics in China, 2015. CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25." }, { "pmid": "29567081", "type": "BACKGROUND", "citation": "Beatty GL, O'Hara MH, Lacey SF, Torigian DA, Nazimuddin F, Chen F, Kulikovskaya IM, Soulen MC, McGarvey M, Nelson AM, Gladney WL, Levine BL, Melenhorst JJ, Plesa G, June CH. Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial. Gastroenterology. 2018 Jul;155(1):29-32. doi: 10.1053/j.gastro.2018.03.029. Epub 2018 Mar 20." } ] } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D010190", "term": "Pancreatic Neoplasms" } ], "ancestors": [ { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT04956640", "orgStudyIdInfo": { "id": "LOXO-RAS-20001" }, "secondaryIdInfos": [ { "id": "2021-000595-12", "type": "EUDRACT_NUMBER" }, { "id": "J3M-OX-JZQA", "type": "OTHER", "domain": "Eli Lilly and Company" }, { "id": "MK-3475-E27/KEYNOTE E27", "type": "OTHER", "domain": "Merck Sharp & Dohme LLC" }, { "id": "2022-502756-31-00", "type": "CTIS" } ], "organization": { "fullName": "Eli Lilly and Company", "class": "INDUSTRY" }, "briefTitle": "Study of LY3537982 in Cancer Patients With a Specific Genetic Mutation (KRAS G12C)", "officialTitle": "A Phase 1/2 Study of LY3537982 in Patients With KRAS G12C-Mutant Advanced Solid Tumors" }, "statusModule": { "statusVerifiedDate": "2025-09", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2021-07-19", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2027-04", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2027-04", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2021-07-02", "studyFirstSubmitQcDate": "2021-07-02", "studyFirstPostDateStruct": { "date": "2021-07-09", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-09-22", "lastUpdatePostDateStruct": { "date": "2025-09-25", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Eli Lilly and Company", "class": "INDUSTRY" }, "collaborators": [ { "name": "Merck Sharp & Dohme LLC", "class": "INDUSTRY" } ] }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "The purpose of this study is to find out whether the study drug, LY3537982, is safe and effective in cancer patients who have a specific genetic mutation (KRAS G12C). Patients must have already received or were not able to tolerate the standard of care, except for specific groups who have not had cancer treatment. The study will last up to approximately 4 years.", "detailedDescription": "This is an open-label, multicenter Phase 1/2 study to evaluate safety, tolerability, and preliminary efficacy of oral LY3537982 in patients with KRAS G12C-mutant solid tumors.\n\nThis study will be conducted in 4 parts: Phase 1a dose escalation, Phase 1b dose expansion, Phase 1b dose optimization, and Phase 2. KRAS G12C mutations will be identified through standard of care testing." }, "conditionsModule": { "conditions": [ "Carcinoma, Non-Small-Cell Lung", "Colorectal Neoplasms", "Endometrial Neoplasms", "Ovarian Neoplasms", "Pancreatic Neoplasms", "Biliary Tract Neoplasms" ], "keywords": [ "Frontline", "1L", "First Line" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "NON_RANDOMIZED", "interventionModel": "SEQUENTIAL", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 540, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "LY3537982 (Dose Escalation)", "type": "EXPERIMENTAL", "description": "LY3537982 administered orally.", "interventionNames": [ "Drug: LY3537982" ] }, { "label": "LY3537982 (Dose Expansion)", "type": "EXPERIMENTAL", "description": "LY3537982 administered orally either alone or with another investigational agent.", "interventionNames": [ "Drug: LY3537982", "Drug: Pembrolizumab", "Drug: Cetuximab", "Drug: Pemetrexed", "Drug: Cisplatin", "Drug: Carboplatin" ] }, { "label": "LY3537982 (Dose Optimization)", "type": "EXPERIMENTAL", "description": "LY3537982 administered orally either alone or with another investigational agent", "interventionNames": [ "Drug: LY3537982", "Drug: Pembrolizumab", "Drug: Cetuximab" ] } ], "interventions": [ { "type": "DRUG", "name": "LY3537982", "description": "Oral", "armGroupLabels": [ "LY3537982 (Dose Escalation)", "LY3537982 (Dose Expansion)", "LY3537982 (Dose Optimization)" ], "otherNames": [ "Olomorasib" ] }, { "type": "DRUG", "name": "Pembrolizumab", "description": "Intravenous", "armGroupLabels": [ "LY3537982 (Dose Expansion)", "LY3537982 (Dose Optimization)" ], "otherNames": [ "KEYTRUDA®" ] }, { "type": "DRUG", "name": "Cetuximab", "description": "Intravenous", "armGroupLabels": [ "LY3537982 (Dose Expansion)", "LY3537982 (Dose Optimization)" ], "otherNames": [ "Erbitux" ] }, { "type": "DRUG", "name": "Pemetrexed", "description": "Intravenous", "armGroupLabels": [ "LY3537982 (Dose Expansion)" ], "otherNames": [ "LY231514", "Alimta" ] }, { "type": "DRUG", "name": "Cisplatin", "description": "Intravenous", "armGroupLabels": [ "LY3537982 (Dose Expansion)" ] }, { "type": "DRUG", "name": "Carboplatin", "description": "Intravenous", "armGroupLabels": [ "LY3537982 (Dose Expansion)" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Phase 1a: To determine the recommended phase 2 dose (RP2D) of LY3537982 monotherapy", "description": "Measured by the number of patients with dose-limiting toxicities (DLTs)", "timeFrame": "Cycle 1 (21 Days)" }, { "measure": "Phase 1b: To assess the safety and tolerability of LY3537982 when administered alone or in combination with other investigational agents", "description": "Measured by the number of patients with dose-limiting toxicities (DLTs)", "timeFrame": "Cycle 1 (21 Days)" }, { "measure": "Phase 1b: To determine the optimal dose of LY3537982 to be administered to treatment-naïve participants with advanced NSCLC in combination with pembrolizumab", "description": "Measured by TEAEs", "timeFrame": "Estimated up to 2 years" }, { "measure": "To determine the optimal dose of LY3537982 to be administered to participants who have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC in combination with cetuximab", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the antitumor activity of LY3537982 monotherapy in participants with advanced pancreatic cancer with KRAS G12C mutation", "timeFrame": "Estimated up to 2 years" } ], "secondaryOutcomes": [ { "measure": "To assess preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Objective response rate (ORR)", "description": "ORR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Duration of Response (DOR)", "description": "DOR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Best Overall Response (BOR)", "description": "BOR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Time to response (TTR)", "description": "TTR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Disease control rate (DCR)", "description": "DCR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Progression-free survival (PFS)", "description": "PFS", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Overall survival (OS)", "description": "OS", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Intracranial DOR based on modified RECIST v1.1 (Certain arms of the study only)", "description": "Intracranial DOR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To assess the preliminary antitumor activity of LY3537982 when administered alone or in combination with other investigational agents: Whole-body ORR based on RECIST v1.1 and modified RECIST v1.1 (Certain arms of the study only)", "description": "Whole-body ORR", "timeFrame": "Estimated up to 2 years" }, { "measure": "To characterize the pharmacokinetics (PK) properties of LY3537982: Area under the plasma concentration versus time curve (AUC)", "description": "PK: AUC of LY3537982", "timeFrame": "Predose estimated up to 2 years" }, { "measure": "To characterize the PK properties of LY3537982: Maximum drug concentration (Cmax)", "description": "PK: Cmax of LY3537982", "timeFrame": "Predose estimated up to 2 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Patients have measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).\n* Patients must have disease with evidence of KRAS G12C mutation in tumor tissue or circulating tumor deoxyribonucleic acid (DNA).\n* Participants must have a histological or a cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and meet cohort-specific criteria.\n* Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.\n* Have adequate organ function.\n* Have discontinued all previous treatments for cancer with resolution of any significant ongoing adverse events (AEs), (except in certain scenarios).\n* Must be able to swallow capsule/tablet.\n* Agree and adhere to contraceptive use, if applicable.\n* For some parts of the study, (i.e., one of the two arms with LY3537982 in combination with pembrolizumab and the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy) histologically or cytologically confirmed Stage IIIB-IIIC or Stage IV NSCLC that is previously untreated in the advanced/metastatic setting and not suitable for curative intent radical surgery or radiation therapy. Previously untreated patients who received adjuvant and neoadjuvant therapy are eligible if the last dose of the systemic treatment was completed at least 6 months prior to enrollment. For untreated patients in the arm with LY3537982 in combination with pembrolizumab noted above, a single cycle of pembrolizumab may be initiated within 21 days prior to enrollment. For untreated patients in the arm of LY3537982 in combination with pembrolizumab, pemetrexed, and platinum therapy, a single cycle of any or all of the drugs other than LY3537982 may be initiated within 21 days prior to enrollment. Start of study treatment may be delayed to allow sufficient time for recovery from treatment-related toxicity.\n* For one part of the study, participants must have received at least one prior oxaliplatin- or irinotecan-containing regimen for advanced or metastatic CRC.\n\nExclusion Criteria:\n\n* Disease suitable for local therapy administered with curative intent.\n* Have an active, ongoing, or untreated infection.\n* Have a serious pre-existing medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.\n* Have a serious cardiac condition.\n* Have a second active primary malignancy or have been diagnosed and/or treated for an additional malignancy within 3 years prior to enrollment.\n* For some parts of the study only: have untreated active central nervous system (CNS) metastases and/or leptomeningeal disease. Patients with treated CNS metastases are eligible for this study if their disease is asymptomatic, radiographically stable for at least 30 days, and they do not require treatment with steroids in the two-week period prior to study treatment. Patients with active CNS metastases are eligible for one part of the study.\n* Have received prior treatment with any KRAS G12C small molecule inhibitor, except in certain scenarios where such prior therapy is allowed as per protocol.\n* The following patients will be excluded from some parts of the study:\n\n * Experienced certain serious side effects with prior immunotherapy.\n * Have an active autoimmune disease that has required systemic anti-autoimmune treatment in the past 2 years.\n * Have received a live vaccine within 30 days prior to the first dose of study drug.\n* Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial through 35 days after the last dose of study medication.\n* Known allergic reaction against any of the components of the study treatments.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or", "role": "CONTACT", "phone": "1-317-615-4559", "email": "LillyTrials@Lilly.com" }, { "name": "Physicians interested in becoming principal investigators please contact", "role": "CONTACT", "email": "clinical_inquiry_hub@lilly.com" } ], "overallOfficials": [ { "name": "Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)", "affiliation": "Eli Lilly and Company", "role": "STUDY_DIRECTOR" } ], "locations": [ { "facility": "University of Alabama at Birmingham", "status": "RECRUITING", "city": "Birmingham", "state": "Alabama", "zip": "35233", "country": "United States", "geoPoint": { "lat": 33.52066, "lon": -86.80249 } }, { "facility": "USC Norris Cancer Hospital", "status": "RECRUITING", "city": "Los Angeles", "state": "California", "zip": "90033", "country": "United States", "geoPoint": { "lat": 34.05223, "lon": -118.24368 } }, { "facility": "Chao Family Comprehensive Cancer Ctr.", "status": "RECRUITING", "city": "Orange", "state": "California", "zip": "92868", "country": "United States", "geoPoint": { "lat": 33.78779, "lon": -117.85311 } }, { "facility": "Yale-New Haven Hospital", "status": "RECRUITING", "city": "New Haven", "state": "Connecticut", "zip": "06510", "country": "United States", "geoPoint": { "lat": 41.30815, "lon": -72.92816 } }, { "facility": "AdventHealth Orlando", "status": "RECRUITING", "city": "Orlando", "state": "Florida", "zip": "32803", "country": "United States", "geoPoint": { "lat": 28.53834, "lon": -81.37924 } }, { "facility": "Florida Cancer Specialists", "status": "RECRUITING", "city": "Sarasota", "state": "Florida", "zip": "34236", "country": "United States", "geoPoint": { "lat": 27.33643, "lon": -82.53065 } }, { "facility": "Indiana Univ Melvin & Bren Simon Cancer Center", "status": "RECRUITING", "city": "Indianapolis", "state": "Indiana", "zip": "46202", "country": "United States", "geoPoint": { "lat": 39.76838, "lon": -86.15804 } }, { "facility": "Community Health Network", "status": "RECRUITING", "city": "Indianapolis", "state": "Indiana", "zip": "46250", "country": "United States", "geoPoint": { "lat": 39.76838, "lon": -86.15804 } }, { "facility": "Mary Bird Perkins Cancer Center", "status": "RECRUITING", "city": "Baton Rouge", "state": "Louisiana", "zip": "70809", "country": "United States", "geoPoint": { "lat": 30.44332, "lon": -91.18747 } }, { "facility": "Massachusetts General Hospital", "status": "RECRUITING", "city": "Boston", "state": "Massachusetts", "zip": "02114", "country": "United States", "geoPoint": { "lat": 42.35843, "lon": -71.05977 } }, { "facility": "Dartmouth-Hitchcock Medical Center", "status": "RECRUITING", "city": "Lebanon", "state": "New Hampshire", "zip": "03756", "country": "United States", "geoPoint": { "lat": 43.64229, "lon": -72.25176 } }, { "facility": "NYU Langone Health- Long Island", "status": "RECRUITING", "city": "Mineola", "state": "New York", "zip": "11501", "country": "United States", "geoPoint": { "lat": 40.74927, "lon": -73.64068 } }, { "facility": "NYU Langone", "status": "RECRUITING", "city": "New York", "state": "New York", "zip": "10016", "country": "United States", "geoPoint": { "lat": 40.71427, "lon": -74.00597 } }, { "facility": "Memorial Sloan Kettering Cancer Center", "status": "RECRUITING", "city": "New York", "state": "New York", "zip": "10065", "country": "United States", "geoPoint": { "lat": 40.71427, "lon": -74.00597 } }, { "facility": "The University of North Carolina at Chapel Hill", "status": "RECRUITING", "city": "Chapel Hill", "state": "North Carolina", "zip": "27599", "country": "United States", "geoPoint": { "lat": 35.9132, "lon": -79.05584 } }, { "facility": "Novant Health Cancer Institute - Elizabeth", "status": "RECRUITING", "city": "Charlotte", "state": "North Carolina", "zip": "28204", "country": "United States", "geoPoint": { "lat": 35.22709, "lon": -80.84313 } }, { "facility": "Novant Health Cancer Institute - Forsyth", "status": "RECRUITING", "city": "Winston-Salem", "state": "North Carolina", "zip": "27103", "country": "United States", "geoPoint": { "lat": 36.09986, "lon": -80.24422 } }, { "facility": "Fox Chase Cancer Center", "status": "RECRUITING", "city": "Philadelphia", "state": "Pennsylvania", "zip": "19111-2497", "country": "United States", "geoPoint": { "lat": 39.95238, "lon": -75.16362 } }, { "facility": "UPMC Hillman Cancer Center", "status": "RECRUITING", "city": "Pittsburgh", "state": "Pennsylvania", "zip": "15232", "country": "United States", "geoPoint": { "lat": 40.44062, "lon": -79.99589 } }, { "facility": "Sarah Cannon Cancer Center", "status": "RECRUITING", "city": "Nashville", "state": "Tennessee", "zip": "37203", "country": "United States", "geoPoint": { "lat": 36.16589, "lon": -86.78444 } }, { "facility": "Vanderbilt Univeristy School of Medicine", "status": "RECRUITING", "city": "Nashville", "state": "Tennessee", "zip": "37212-6303", "country": "United States", "geoPoint": { "lat": 36.16589, "lon": -86.78444 } }, { "facility": "South Texas Accelerated Research Therapeutics (START)", "status": "RECRUITING", "city": "San Antonio", "state": "Texas", "zip": "78229-3307", "country": "United States", "geoPoint": { "lat": 29.42412, "lon": -98.49363 } }, { "facility": "START Mountain Region", "status": "RECRUITING", "city": "West Valley City", "state": "Utah", "zip": "84119", "country": "United States", "geoPoint": { "lat": 40.69161, "lon": -112.00105 } }, { "facility": "Inova Health System IRB", "status": "RECRUITING", "city": "Fairfax", "state": "Virginia", "zip": "22031", "country": "United States", "geoPoint": { "lat": 38.84622, "lon": -77.30637 } }, { "facility": "USO-Virginia Cancer Specialists, PC", "status": "RECRUITING", "city": "Fairfax", "state": "Virginia", "zip": "22031", "country": "United States", "geoPoint": { "lat": 38.84622, "lon": -77.30637 } }, { "facility": "University of Wisconsin-Madison Hospital and Health Clinic", "status": "RECRUITING", "city": "Madison", "state": "Wisconsin", "zip": "53792-4108", "country": "United States", "geoPoint": { "lat": 43.07305, "lon": -89.40123 } }, { "facility": "Royal North Shore Hospital", "status": "RECRUITING", "city": "St Leonards", "state": "New South Wales", "zip": "2065", "country": "Australia", "geoPoint": { "lat": -33.82344, "lon": 151.19836 } }, { "facility": "St Vincent's Hospital Sydney", "status": "RECRUITING", "city": "Sydney", "state": "New South Wales", "zip": "2010", "country": "Australia", "geoPoint": { "lat": -33.86785, "lon": 151.20732 } }, { "facility": "Cancer Research SA", "status": "RECRUITING", "city": "Adelaide", "state": "South Australia", "zip": "5000", "country": "Australia", "geoPoint": { "lat": -34.92866, "lon": 138.59863 } }, { "facility": "Peninsula and Southeast Oncology", "status": "RECRUITING", "city": "Frankston", "state": "Victoria", "zip": "3199", "country": "Australia", "geoPoint": { "lat": -38.14458, "lon": 145.12291 } }, { "facility": "Linear Clinical Research", "status": "RECRUITING", "city": "Nedlands", "state": "Western Australia", "zip": "6009", "country": "Australia", "geoPoint": { "lat": -31.98184, "lon": 115.8073 } }, { "facility": "Cross Cancer Institute", "status": "RECRUITING", "city": "Edmonton", "state": "Alberta", "zip": "T6G 1Z2", "country": "Canada", "geoPoint": { "lat": 53.55014, "lon": -113.46871 } }, { "facility": "Princess Margaret Hospital (Ontario)", "status": "RECRUITING", "city": "Toronto", "state": "Ontario", "zip": "M4X 1K9", "country": "Canada", "geoPoint": { "lat": 43.70643, "lon": -79.39864 } }, { "facility": "Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest", "status": "RECRUITING", "city": "Bordeaux", "state": "Aquitaine", "zip": "33076", "country": "France", "geoPoint": { "lat": 44.84124, "lon": -0.58046 } }, { "facility": "Centre Leon Berard", "status": "RECRUITING", "city": "Lyon", "state": "Auvergne-Rhône-Alpes", "zip": "69008", "country": "France", "geoPoint": { "lat": 45.74906, "lon": 4.84789 } }, { "facility": "Institut du Cancer de Montpellier - Val d'aurelle", "status": "RECRUITING", "city": "Montpellier", "zip": "34298", "country": "France", "geoPoint": { "lat": 43.61093, "lon": 3.87635 } }, { "facility": "Institut Claudius Regaud - IUCT Oncopole", "status": "RECRUITING", "city": "Toulouse", "zip": "31052", "country": "France", "geoPoint": { "lat": 43.60426, "lon": 1.44367 } }, { "facility": "Gustave Roussy", "status": "RECRUITING", "city": "Villejuif", "zip": "94805", "country": "France", "geoPoint": { "lat": 48.7939, "lon": 2.35992 } }, { "facility": "Aichi Cancer Center Hospital", "status": "RECRUITING", "city": "Nagoya", "state": "Aichi-ken", "zip": "464-8681", "country": "Japan", "geoPoint": { "lat": 35.18147, "lon": 136.90641 } }, { "facility": "National Cancer Center Hospital East", "status": "RECRUITING", "city": "Kashiwa", "state": "Chiba", "zip": "277-8577", "country": "Japan", "geoPoint": { "lat": 35.86224, "lon": 139.97732 } }, { "facility": "Hokkaido University Hospital", "status": "RECRUITING", "city": "Sapporo", "state": "Hokkaido", "zip": "060-8648", "country": "Japan", "geoPoint": { "lat": 43.06667, "lon": 141.35 } }, { "facility": "Kanazawa University Hospital", "status": "RECRUITING", "city": "Kanazawa", "state": "Ishikawa-ken", "zip": "920", "country": "Japan", "geoPoint": { "lat": 36.6, "lon": 136.61667 } }, { "facility": "National Cancer Center Hospital", "status": "RECRUITING", "city": "Chuo-ku", "state": "Tokyo", "zip": "104-0045", "country": "Japan" }, { "facility": "Wakayama Medical University Hospital", "status": "RECRUITING", "city": "Wakayama", "zip": "641-8510", "country": "Japan", "geoPoint": { "lat": 34.23333, "lon": 135.16667 } }, { "facility": "National Cancer Center", "status": "RECRUITING", "city": "Goyang-si", "state": "Gyeonggi-do", "zip": "10408", "country": "South Korea", "geoPoint": { "lat": 37.65639, "lon": 126.835 } }, { "facility": "The Catholic University of Korea, St. Vincent's Hospital", "status": "RECRUITING", "city": "Suwon", "state": "Gyeonggi-do", "zip": "16247", "country": "South Korea", "geoPoint": { "lat": 37.29111, "lon": 127.00889 } }, { "facility": "Chonnam National University Hwasun Hospital", "status": "RECRUITING", "city": "Hwasun-gun", "state": "Jeonranamdo", "zip": "58128", "country": "South Korea" }, { "facility": "Seoul National University Hospital", "status": "RECRUITING", "city": "Seoul", "state": "Korea", "zip": "03080", "country": "South Korea", "geoPoint": { "lat": 37.566, "lon": 126.9784 } }, { "facility": "Asan Medical Center", "status": "RECRUITING", "city": "Seoul", "state": "Korea", "zip": "05505", "country": "South Korea", "geoPoint": { "lat": 37.566, "lon": 126.9784 } } ] }, "referencesModule": { "seeAlsoLinks": [ { "label": "Study of LY3537982 in Cancer Patients with a Specific Genetic Mutation (KRAS G12C)", "url": "https://trials.lilly.com/en-US/trial/295242" } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D002289", "term": "Carcinoma, Non-Small-Cell Lung" }, { "id": "D015179", "term": "Colorectal Neoplasms" }, { "id": "D016889", "term": "Endometrial Neoplasms" }, { "id": "D010051", "term": "Ovarian Neoplasms" }, { "id": "D010190", "term": "Pancreatic Neoplasms" }, { "id": "D001661", "term": "Biliary Tract Neoplasms" } ], "ancestors": [ { "id": "D002283", "term": "Carcinoma, Bronchogenic" }, { "id": "D001984", "term": "Bronchial Neoplasms" }, { "id": "D008175", "term": "Lung Neoplasms" }, { "id": "D012142", "term": "Respiratory Tract Neoplasms" }, { "id": "D013899", "term": "Thoracic Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D008171", "term": "Lung Diseases" }, { "id": "D012140", "term": "Respiratory Tract Diseases" }, { "id": "D007414", "term": "Intestinal Neoplasms" }, { "id": "D005770", "term": "Gastrointestinal Neoplasms" }, { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D005767", "term": "Gastrointestinal Diseases" }, { "id": "D003108", "term": "Colonic Diseases" }, { "id": "D007410", "term": "Intestinal Diseases" }, { "id": "D012002", "term": "Rectal Diseases" }, { "id": "D014594", "term": "Uterine Neoplasms" }, { "id": "D005833", "term": "Genital Neoplasms, Female" }, { "id": "D014565", "term": "Urogenital Neoplasms" }, { "id": "D014591", "term": "Uterine Diseases" }, { "id": "D005831", "term": "Genital Diseases, Female" }, { "id": "D052776", "term": "Female Urogenital Diseases" }, { "id": "D005261", "term": "Female Urogenital Diseases and Pregnancy Complications" }, { "id": "D000091642", "term": "Urogenital Diseases" }, { "id": "D000091662", "term": "Genital Diseases" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D010049", "term": "Ovarian Diseases" }, { "id": "D000291", "term": "Adnexal Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" }, { "id": "D006058", "term": "Gonadal Disorders" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D001660", "term": "Biliary Tract Diseases" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C582435", "term": "pembrolizumab" }, { "id": "D000068818", "term": "Cetuximab" }, { "id": "D000068437", "term": "Pemetrexed" }, { "id": "D002945", "term": "Cisplatin" }, { "id": "D016190", "term": "Carboplatin" } ], "ancestors": [ { "id": "D061067", "term": "Antibodies, Monoclonal, Humanized" }, { "id": "D000911", "term": "Antibodies, Monoclonal" }, { "id": "D000906", "term": "Antibodies" }, { "id": "D007136", "term": "Immunoglobulins" }, { "id": "D007162", "term": "Immunoproteins" }, { "id": "D001798", "term": "Blood Proteins" }, { "id": "D011506", "term": "Proteins" }, { "id": "D000602", "term": "Amino Acids, Peptides, and Proteins" }, { "id": "D012712", "term": "Serum Globulins" }, { "id": "D005916", "term": "Globulins" }, { "id": "D006147", "term": "Guanine" }, { "id": "D007042", "term": "Hypoxanthines" }, { "id": "D011688", "term": "Purinones" }, { "id": "D011687", "term": "Purines" }, { "id": "D006574", "term": "Heterocyclic Compounds, 2-Ring" }, { "id": "D000072471", "term": "Heterocyclic Compounds, Fused-Ring" }, { "id": "D006571", "term": "Heterocyclic Compounds" }, { "id": "D005971", "term": "Glutamates" }, { "id": "D024342", "term": "Amino Acids, Acidic" }, { "id": "D000596", "term": "Amino Acids" }, { "id": "D000600", "term": "Amino Acids, Dicarboxylic" }, { "id": "D017606", "term": "Chlorine Compounds" }, { "id": "D007287", "term": "Inorganic Chemicals" }, { "id": "D017672", "term": "Nitrogen Compounds" }, { "id": "D017671", "term": "Platinum Compounds" }, { "id": "D056831", "term": "Coordination Complexes" }, { "id": "D009930", "term": "Organic Chemicals" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT06008288", "orgStudyIdInfo": { "id": "JAB-21822-2001" }, "organization": { "fullName": "Allist Pharmaceuticals, Inc.", "class": "INDUSTRY" }, "briefTitle": "A Phase II Study Evaluating JAB-21822 Monotherapy in Adult Patients With Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation.", "officialTitle": "A Single-arm, Multicenter, Open-label Phase II Clinical Study Evaluating the Efficacy and Safety of JAB-21822 Monotherapy in Patients With Locally Advanced or Metastatic Pancreatic Cancer and Other Solid Tumors Harboring the KRAS p.G12C Mutation." }, "statusModule": { "statusVerifiedDate": "2024-10", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2023-10-27", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2026-12-31", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2027-12-31", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2023-08-18", "studyFirstSubmitQcDate": "2023-08-18", "studyFirstPostDateStruct": { "date": "2023-08-23", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-08-04", "lastUpdatePostDateStruct": { "date": "2025-08-07", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Allist Pharmaceuticals, Inc.", "class": "INDUSTRY" } }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false, "isUsExport": false }, "descriptionModule": { "briefSummary": "Patients with other advanced solid tumors (excluding NSCLC and CRC) who have progressed after prior systemic therapy or are intolerant and lack satisfactory alternative treatment options, aiming to evaluate the efficacy and safety of Glecirasib in these patients.", "detailedDescription": "This study is a single-arm, multicenter, open-label, basket-design, pivotal phase II trial targeting adult patients with locally advanced or metastatic solid tumors harboring the KRAS p.G12C mutation. The included populations are:\n\n* Patients with advanced pancreatic cancer who have progressed or are intolerant to prior gemcitabine-based chemotherapy regimens or FOLFIRINOX/mFOLFIRINOX/NALIRIFOX treatments.\n* Patients with other advanced solid tumors (excluding NSCLC and CRC) who have progressed after prior systemic therapies or are intolerant and lack satisfactory alternative treatment options.\n\nThe study aims to evaluate the efficacy and safety of Glecirasib in these patient populations." }, "conditionsModule": { "conditions": [ "KRAS P.G12C", "Pancreatic Cancer", "Solid Tumor" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE2" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 88, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "JAB-21822", "type": "EXPERIMENTAL", "description": "Monotherapy", "interventionNames": [ "Drug: JAB-21822" ] } ], "interventions": [ { "type": "DRUG", "name": "JAB-21822", "description": "800mg, orally QD with 21 days each cycle, treatment till disease progression or intolerable toxicity or withdraw for other reasons", "armGroupLabels": [ "JAB-21822" ], "otherNames": [ "Glecirasib" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Objective response rate (ORR) by independent central radiological review (IRC) according to RECIST 1.1.", "description": "ORR is defined as the proportion of participants with confirmed complete response or partial response by IRC according to RECIST 1.1.", "timeFrame": "Approximately 1.5 years" } ], "secondaryOutcomes": [ { "measure": "Duration of response (DOR)", "description": "DOR is defined as the time from date of the first objective tumor response (CR or PR) to the first documentation of either Progression of Disease (PD) or death due to any cause, whichever occurs first.", "timeFrame": "Approximately 1.5 years" }, { "measure": "Time to response (TTR) by IRC according to RECIST 1.1", "description": "TTR is defined as the duration of time between the date of the first dose and the date of first documented response of either CR or PR.", "timeFrame": "Approximately 1.5 years" }, { "measure": "Progression-free survival (PFS) by IRC according to RECIST 1.1", "description": "PFS is defined as time from the first dose until disease progression or death from any cause, whichever occurs first.", "timeFrame": "Approximately 1.5 years" }, { "measure": "Disease control rate (DCR) by IRC according to RECIST 1.1", "description": "DCR is defined as the proportion of participants with BOR of CR or PR or stable disease (SD)", "timeFrame": "Approximately 1.5 years" }, { "measure": "CA19-9 response rate (Applicable only to pancreatic cancer)", "description": "CA19-9 response rate is defined as the proportion of participants with CA19-9 response (achieving ≥50% decrease in CA19-9 serum levels).", "timeFrame": "Approximately 1.5 years" }, { "measure": "Overall survival (OS)", "description": "OS is defined as time from date of the first dose to date of death due to any cause.", "timeFrame": "Approximately 2.0 years" }, { "measure": "Number of participants with adverse events", "description": "Participants will be assessed for incidence and severity of AEs according to NCI-CTCAE 5.0 criteria", "timeFrame": "Approximately 1.5 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Patients with the KRAS p.G12C mutation confirmed through testing using prospectively validated companion diagnostic reagents or clinical trial assay (CTA) methods.\n* Histologically or cytologically confirmed locally advanced unresectable or metastatic solid tumors (excluding NSCLC and CRC).\n* Patients with pancreatic cancer must have progressed or been intolerant to prior gemcitabine-based chemotherapy regimens or FOLFIRINOX/mFOLFIRINOX/NALIRIFOX treatment. Patients with other types of solid tumors must have progressed or been intolerant to prior systemic therapies and lack satisfactory alternative treatment options.\n\nExclusion Criteria:\n\n* Previously received a KRAS G12C inhibitor.\n* History of interstitial lung disease, non-infectious pneumonia, or uncontrolled lung disease (including pulmonary fibrosis, acute lung disease, etc.) with clinical symptoms.\n* Uncontrolled pleural effusion, pericardial effusion, or ascites.\n* Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 electrocardiograms.\n* Use of a drug with known risk of torsades de points (TdP) within 14 days prior to the first dose.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Shanghai Allist Pharmaceuticals Co., Ltd", "role": "CONTACT", "phone": "86-21-80423288", "email": "zhenhua.gong@allist.com.cn" } ], "overallOfficials": [ { "name": "Shanghai Allist Pharmaceuticals", "affiliation": "Shanghai Allist Pharmaceuticals Co.,Ltd.", "role": "STUDY_DIRECTOR" } ], "locations": [ { "facility": "Anhui Provincial Cancer Hospital", "status": "RECRUITING", "city": "Hefei", "state": "Anhui", "country": "China", "geoPoint": { "lat": 31.86389, "lon": 117.28083 } }, { "facility": "Beijing Cancer Hospital", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100142", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Peking Union Medical College Hospital", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "zip": "100730", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Beijing Tsinghua Changgung Hospital", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Cancer Hospital Chinese Academy of Medical Sciences", "status": "RECRUITING", "city": "Beijing", "state": "Beijing Municipality", "country": "China", "geoPoint": { "lat": 39.9075, "lon": 116.39723 } }, { "facility": "Fujian Cancer Hospital", "status": "RECRUITING", "city": "Fuzhou", "state": "Fujian", "country": "China", "geoPoint": { "lat": 26.06139, "lon": 119.30611 } }, { "facility": "Sun Yat-sen Memorial Hospital, Sun Yat-sen University", "status": "RECRUITING", "city": "Guangzhou", "state": "Guangdong", "country": "China", "geoPoint": { "lat": 23.11667, "lon": 113.25 } }, { "facility": "Sun Yat-Sen University Cancer Center", "status": "RECRUITING", "city": "Guangzhou", "state": "Guangdong", "country": "China", "geoPoint": { "lat": 23.11667, "lon": 113.25 } }, { "facility": "The First Affiliated Hospital of Sun, Yat-sen University", "status": "RECRUITING", "city": "Guangzhou", "state": "Guangdong", "country": "China", "geoPoint": { "lat": 23.11667, "lon": 113.25 } }, { "facility": "Guangxi Medical University Cancer Hospital", "status": "RECRUITING", "city": "Nanning", "state": "Guangxi", "country": "China", "geoPoint": { "lat": 22.81667, "lon": 108.31667 } }, { "facility": "Harbin Medical University Cancer Hospital", "status": "RECRUITING", "city": "Harbin", "state": "Heilongjiang", "country": "China", "geoPoint": { "lat": 45.75, "lon": 126.65 } }, { "facility": "Henan Cancer Hospital", "status": "RECRUITING", "city": "Zhengzhou", "state": "Henan", "country": "China", "geoPoint": { "lat": 34.75778, "lon": 113.64861 } }, { "facility": "The First Affiliated Hospital of Zhengzhou University", "status": "RECRUITING", "city": "Zhengzhou", "state": "Henan", "country": "China", "geoPoint": { "lat": 34.75778, "lon": 113.64861 } }, { "facility": "Hubei Cancer Hospital", "status": "RECRUITING", "city": "Wuhan", "state": "Hubei", "country": "China", "geoPoint": { "lat": 30.58333, "lon": 114.26667 } }, { "facility": "Union Hospital, Tongji Medical College, Huazhong University of Science and Technology", "status": "RECRUITING", "city": "Wuhan", "state": "Hubei", "country": "China", "geoPoint": { "lat": 30.58333, "lon": 114.26667 } }, { "facility": "Hunan Cancer Hospital", "status": "RECRUITING", "city": "Changsha", "state": "Hunan", "country": "China", "geoPoint": { "lat": 28.19874, "lon": 112.97087 } }, { "facility": "Hunan Provincial People's Hospital", "status": "RECRUITING", "city": "Changsha", "state": "Hunan", "country": "China", "geoPoint": { "lat": 28.19874, "lon": 112.97087 } }, { "facility": "Jiangsu Cancer Hospital", "status": "RECRUITING", "city": "Nanjing", "state": "Jiangsu", "country": "China", "geoPoint": { "lat": 32.06167, "lon": 118.77778 } }, { "facility": "Jiangsu Province Hospital", "status": "RECRUITING", "city": "Nanjing", "state": "Jiangsu", "country": "China", "geoPoint": { "lat": 32.06167, "lon": 118.77778 } }, { "facility": "The First Affiliated Hospital of Nanchang University", "status": "RECRUITING", "city": "Nanchang", "state": "Jiangxi", "country": "China", "geoPoint": { "lat": 28.68396, "lon": 115.85306 } }, { "facility": "The First Hospital of China Medical University", "status": "RECRUITING", "city": "Shenyang", "state": "Liaoning", "country": "China", "geoPoint": { "lat": 41.79222, "lon": 123.43278 } }, { "facility": "Shandong Cancer Hospital", "status": "RECRUITING", "city": "Jinan", "state": "Shandong", "country": "China", "geoPoint": { "lat": 36.66833, "lon": 116.99722 } }, { "facility": "The Affiliated Hospital of Qingdao University", "status": "NOT_YET_RECRUITING", "city": "Qingdao", "state": "Shandong", "country": "China", "geoPoint": { "lat": 36.06488, "lon": 120.38042 } }, { "facility": "Huashan Hospital, Fudan University", "status": "RECRUITING", "city": "Shanghai", "state": "Shanghai Municipality", "country": "China", "geoPoint": { "lat": 31.22222, "lon": 121.45806 } }, { "facility": "Shanghai Changhai Hospital", "status": "RECRUITING", "city": "Shanghai", "state": "Shanghai Municipality", "country": "China", "geoPoint": { "lat": 31.22222, "lon": 121.45806 } }, { "facility": "The First Affiliated Hospital of Xi'an Jiaotong University", "status": "RECRUITING", "city": "Xi’an", "state": "Shanxi", "country": "China", "geoPoint": { "lat": 35.99785, "lon": 113.52486 } }, { "facility": "West China Hospital of Sichuan University", "status": "RECRUITING", "city": "Chengdu", "state": "Sichuan", "country": "China", "geoPoint": { "lat": 30.66667, "lon": 104.06667 } }, { "facility": "Tianjin Medical University Cancer Institute＆Hospital", "status": "RECRUITING", "city": "Tianjin", "state": "Tianjin Municipality", "country": "China", "geoPoint": { "lat": 39.14222, "lon": 117.17667 } }, { "facility": "The First Affiliated Hospital, Zhejiang University School of Medicine", "status": "NOT_YET_RECRUITING", "city": "Hangzhou", "state": "Zhejiang", "country": "China", "geoPoint": { "lat": 30.29365, "lon": 120.16142 } }, { "facility": "Zhejiang Cancer Hospital", "status": "RECRUITING", "city": "Hangzhou", "state": "Zhejiang", "country": "China", "geoPoint": { "lat": 30.29365, "lon": 120.16142 } }, { "facility": "Zhejiang Provincial People's Hospital", "status": "RECRUITING", "city": "Hangzhou", "state": "Zhejiang", "country": "China", "geoPoint": { "lat": 30.29365, "lon": 120.16142 } } ] } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D010190", "term": "Pancreatic Neoplasms" } ], "ancestors": [ { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT06898385", "orgStudyIdInfo": { "id": "IX001 TCR-T" }, "organization": { "fullName": "Sun Yat-sen University", "class": "OTHER" }, "briefTitle": "A Phase I Clinical Study of IX001 TCR-T Injection in the Treatment of Advanced Pancreatic Cancer Patients With KRAS G12V Mutation", "officialTitle": "A Phase I Clinical Study of IX001 TCR-T Injection in the Treatment of Advanced Pancreatic Cancer Patients With KRAS G12V Mutation", "acronym": "IX001 TCR-T" }, "statusModule": { "statusVerifiedDate": "2025-05", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2025-03-27", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2027-03-27", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2027-09-27", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2025-03-21", "studyFirstSubmitQcDate": "2025-03-21", "studyFirstPostDateStruct": { "date": "2025-03-27", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-05-24", "lastUpdatePostDateStruct": { "date": "2025-05-30", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "PRINCIPAL_INVESTIGATOR", "investigatorFullName": "Yuhong Li", "investigatorTitle": "Clinical Professor", "investigatorAffiliation": "Sun Yat-sen University" }, "leadSponsor": { "name": "Sun Yat-sen University", "class": "OTHER" }, "collaborators": [ { "name": "ImmuXell Biotech Ltd.", "class": "UNKNOWN" } ] }, "oversightModule": { "oversightHasDmc": false, "isFdaRegulatedDrug": false, "isFdaRegulatedDevice": false, "isUsExport": false }, "descriptionModule": { "briefSummary": "This is a single-arm, open-label clinical study to evaluate the safety, tolerability and preliminary efficacy of IX001 TCR-T injection in advanced pancreatic cancer patients with KRAS G12V mutation.", "detailedDescription": "This study will enroll participants with advanced pancreatic cancer patients with KRAS G12V mutation. The study consists of screening period, leukapheresis period, lymphodepletion period, treatment period, observation period and follow-up period. A total of 9-12 evaluable patients are planned to be recruited. The study is planned to be conducted using the "3 + 3" dose escalation design in two dose groups, and a single dose of the study drug will be administered at the dose levels of 3 × 10\^9 ± 30% cells and 1 × 10\^10 ± 30% cells. Subjects will be enrolled sequentially and treated by IX001 TCR-T injection at the corresponding planned dose level. All subjects who have received IX001 TCR-T injection will be followed for safety and efficacy up to 2 years." }, "conditionsModule": { "conditions": [ "Pancreatic Cancer" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "interventionModelDescription": "IX001 TCR-T injection", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 9, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "IX001 TCR-T injection", "type": "EXPERIMENTAL", "description": "IX001 TCR-T injection targeted for KRAS mutation", "interventionNames": [ "Biological: IX001 TCR-T injection", "Drug: Fludarabine", "Drug: Cyclophosphamide" ] } ], "interventions": [ { "type": "BIOLOGICAL", "name": "IX001 TCR-T injection", "description": "IX001 TCR-T injection will be administered intravenously after lymphodepletion.", "armGroupLabels": [ "IX001 TCR-T injection" ] }, { "type": "DRUG", "name": "Fludarabine", "description": "Fludarabine is used for lymphodepletion.", "armGroupLabels": [ "IX001 TCR-T injection" ], "otherNames": [ "Fludara" ] }, { "type": "DRUG", "name": "Cyclophosphamide", "description": "Cyclophosphamide is used for lymphodepletion.", "armGroupLabels": [ "IX001 TCR-T injection" ], "otherNames": [ "Endoxan" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Dose-limiting Toxicity (DLT)", "description": "Proportion of patients with DLT", "timeFrame": "4 weeks" }, { "measure": "Adverse Events (AEs)", "description": "Incidence and severity of adverse events", "timeFrame": "2 years" }, { "measure": "Serious Adverse Events (SAEs)", "description": "Incidence and severity of serious adverse events", "timeFrame": "2 years" } ], "secondaryOutcomes": [ { "measure": "Objective Response Rate (ORR)", "description": "The percentage of participants who achieved Complete Response (CR) or Partial Response (PR) based on RECIST version 1.1", "timeFrame": "2 years" }, { "measure": "Disease Control Rate (DCR)", "description": "The percentage of participants who achieved Complete Response (CR) or Partial Response (PR) or Stable disease (SD) based on RECIST version 1.1", "timeFrame": "2 years" }, { "measure": "Changes in Serum Tumor Markers compared to Baseline", "description": "Changes of tumor markers in serum detected by immunofluorescence compared to baseline level, including carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen (CEA), and carbohydrate antigen 12-5 (CA12-5)", "timeFrame": "2 years" }, { "measure": "Duration of response (DOR)", "description": "DOR is defined as the time from the first evaluation of a tumor as CR or PR to the first evaluation as progressive disease (PD) or death from any cause", "timeFrame": "2 years" }, { "measure": "Time to response (TTR)", "description": "TTR is defined as the time between cell infusion and initial disease assessment as CR or PR", "timeFrame": "2 years" }, { "measure": "Progression-free survival (PFS)", "description": "PFS is defined as the time from the date of cell infusion until the date of tumor progression or death from any cause", "timeFrame": "2 years" }, { "measure": "Overall survival (OS)", "description": "OS is defined as the time between the date of cell infusion and the death of the patient for any reason", "timeFrame": "2 years" }, { "measure": "TCR gene copies", "description": "TCR gene copies detected by quantitative polymerase chain reaction (qPCR) in peripheral blood", "timeFrame": "2 years" }, { "measure": "TCR-T cell counts", "description": "TCR-T cell counts detected by flow cytometry in peripheral blood", "timeFrame": "2 years" }, { "measure": "Pharmacodynamic of IX001 TCR-T injection", "description": "Peak TCR-T cell count (Cmax), Time to peak (Tmax) ,Area under the peripheral blood concentration versus time curve (AUC)", "timeFrame": "2 years" }, { "measure": "Changes in cytokine level", "description": "Calculate the change of cytokine level in peripheral blood after IX001 TCR-T injection infusion. Cytokines include interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ), etc", "timeFrame": "2 years" }, { "measure": "Changes in lymphocyte subpopulations", "description": "Calculate the change of lymphocyte subpopulations in peripheral blood by flow cytometry after IX001 TCR-T injection infusion. lymphocyte subpopulations include CD3+T cell, CD4+T cell,CD8+T cell, etc", "timeFrame": "2 years" }, { "measure": "Proportion of patients with anti-IX001 antibodies", "description": "Anti-IX001 TCR-T injection Antibodies in peripheral blood after IX001 TCR-T injection infusion.", "timeFrame": "2 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* 1\. Voluntary signing of an informed consent form (for Human Leukocyte Antigen (HLA) typing and tumor gene mutation test, and main screening)\n* 2\. Males or females, aged 18-75 years (inclusive)\n* 3\. Patients with pathologically (histopathologically) or cytologically confirmed pancreatic ductal adenocarcinoma\n* 4\. Patients with unresectable locally advanced or metastatic disease who fail standard of care, i.e., patients who have progression after prior gemcitabine-containing chemotherapy or FOLFIRINOX (oxaliplatin + irinotecan + calcium folinate + 5-FU) or NALIRIFOX (irinotecan liposome + oxaliplatin + calcium folinate + 5-FU) regimen, including those who have progression within 6 months after the end of neoadjuvant/adjuvant therapy\n* 5\. At least one measurable lesion (according to RECIST 1.1 criteria), specifically: longest diameter of ≥10 mm for non lymph node lesions or shortest diameter of ≥15 mm for lymph node lesions (tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable, unless unequivocal progression of the lesion is demonstrated by an evidence)\n* 6\. Patients with tumor tissue or peripheral blood tested positive for KRAS-G12V mutation and expression of matching HLA-A\11:01 subtype\n 7\. Eastern Cooperative Oncology Group (ECOG) ≤ 1\n* 8\. Life expectancy ≥3 months\n* 9\. Adequate functional reserve of organs: A) Hematology requirements (no blood transfusion or hematopoietic stimulating factor treatment within 14 days): Absolute neutrophil count ≥ 1.5×10\^9/L; Platelet count ≥ 75×10\^9/L, hemoglobin \> 90 g/dL; Absolute lymphocyte count ≥ 0.5×10\^9/L; B) Blood Biochemistry Requirements: Alanine aminotransferase ≤ 3 × upper limit of normal（ULN） (≤ 5 × ULN for patients with liver metastases); Aspartate aminotransferase ≤ 3 × ULN (≤ 5 × ULN for patients with liver metastases); Creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min; Serum total bilirubin ≤ 1.5 × ULN; C) Coagulation requirements: Partial thromboplastin activity time (APTT) ≤ 1.5 × ULN; International normalized ratio (INR) ≤1.5 × ULN; D) Left ventricular ejection fraction (LVEF) ≥ 50% and no clinically significant pericardial effusion as diagnosed by echocardiography; E) No clinically significant electrocardiographic abnormality; F) Basic oxygen saturation is \>92% under the indoor natural air environment.\n* 10\. Women of childbearing age must be negative for blood Human Chorionic Gonadotropin (HCG) pregnancy test (by immunofluorescence method) at screening and baseline periods, and agree to use effective contraception for at least 1 year after infusion; and male subjects whose partners are women of childbearing age must agree to use effective barrier contraception methods and avoid sperm donation for at least 1 year after infusion.\n\nExclusion Criteria:\n\n* 1\. Other malignancies (except non-melanoma skin cancer with the disease-free survival of more than 5 years and cervical carcinoma in situ, bladder cancer, or breast cancer)\n* 2\. History of organ transplantation\n* 3\. A history of mental disorders, which may affect compliance with this protocol or lead to failure in signing the Informed Consent Forms(ICF)\n* 4\. A history of autoimmune diseases (e.g., Crohn's disease, rheumatoid arthritis and systemic lupus erythematosus) requiring systemic immunosuppressive/systemic disease-modulating drugs\n* 5\. Poorly controlled hypertension with drug (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg) or occurrence of grade III-IV heart failure or myocardial infarction, cardiac angioplasty or stent placement, unstable angina pectoris, or other clinically significant heart diseases within one year prior to signing the ICF; QTc interval \>450 ms for males or QTc interval \>470 ms for females during screening (QTc interval calculated using the Fridericia formula)\n* 6\. Presence of any indwelling catheter or drainage tube (e.g., percutaneous nephrostomy tube, indwelling catheter, bile drainage tube or pleural/peritoneal/pericardial catheter), except any dedicated central venous catheter\n* 7\. Symptomatic intracranial metastases, or moderate to severe ascites or pleural effusion requiring drainage to relieve symptoms\n* 8\. A history of or any central nervous system disorders, such as epileptic seizure, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease involving the central nervous system within the past 6 months\n* 9\. A positive result obtained in any of the following virological tests: A) Antibody to human immunodeficiency virus (HIV antibody); B) Hepatitis C virus antibody (HCV antibody), with a positive result for hepatitis C virus ribonucleic acid (HCV RNA); C) Positive for hepatitis B surface antigen (HBsAg); or positive for hepatitis B core antibody (HBcAb) and positive for hepatitis B virus deoxyribonucleic acid (HBV DNA) copies ≥2000 IU/mL; D) Treponema pallidum antibody (TP antibody) and positive for unheated serum reagin test;\n* 10\. Fungal, bacterial, viral or other infections or suspected fungal, bacterial, viral or other infections that cannot be controlled or require intravenous administration\n* 11\. Significant tendency for bleeding, such as active gastrointestinal bleeding, coagulation disorders\n* 12\. Deep vein thrombosis requiring treatment within the past 6 months, unless the risk of thrombosis is acceptable after treatment, as assessed by the investigator\n* 13\. Interstitial lung disease (such as interstitial pneumonia, pulmonary fibrosis), or a history of clinically significant respiratory system diseases at screening\n* 14\. Use of granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) within 2 weeks prior to leukapheresis\n* 15\. Receipt of gene therapy or other cell therapies within the past 6 months\n* 16\. Participation in any other clinical studies within 28 days prior to signing the master informed consent form, or the date of signing the master informed consent form still within 5 half-lives of the drug from the last dose in the last clinical study (whichever is longer)\n* 17\. Patients with poor compliance due to physiological, family, social, geographic and other factors, and failure to follow the study protocol and the follow-up plan\n* 18\. Patients with contraindications to drugs used in the study\n* 19\. Comorbidities requiring treatment with systemic corticosteroids (dexamethasone at a dose of ≥ 5 mg/day or other corticosteroids at the equivalent dose) or other immunosuppressive drugs after initiation of the study treatment, as judged by the investigator\n* 20\. Women who are breastfeeding and are unwilling to stop breastfeeding\n* 21\. Any other conditions that are, in the opinion of the investigator, not suitable for enrollment", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "maximumAge": "75 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Yuhong Li", "role": "CONTACT", "phone": "87342487", "phoneExt": "020", "email": "liyh@sysucc.org.cn" } ], "locations": [ { "facility": "Sun Yat-sen University Cancer Center", "status": "RECRUITING", "city": "Guangzhou", "state": "Guangdong", "zip": "510060", "country": "China", "contacts": [ { "name": "Li Yuhong, MD", "role": "CONTACT", "phone": "020-87342487", "email": "liyh@sysucc.org.cn" }, { "name": "Li Yuhong, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 23.11667, "lon": 113.25 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "UNDECIDED" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D010190", "term": "Pancreatic Neoplasms" } ], "ancestors": [ { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C024352", "term": "fludarabine" }, { "id": "C042382", "term": "fludarabine phosphate" }, { "id": "D003520", "term": "Cyclophosphamide" } ], "ancestors": [ { "id": "D010752", "term": "Phosphoramide Mustards" }, { "id": "D009588", "term": "Nitrogen Mustard Compounds" }, { "id": "D009150", "term": "Mustard Compounds" }, { "id": "D006846", "term": "Hydrocarbons, Halogenated" }, { "id": "D006838", "term": "Hydrocarbons" }, { "id": "D009930", "term": "Organic Chemicals" }, { "id": "D063088", "term": "Phosphoramides" }, { "id": "D009943", "term": "Organophosphorus Compounds" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT05786924", "orgStudyIdInfo": { "id": "BDTX-4933-101" }, "secondaryIdInfos": [ { "id": "2025-523474-16-00", "type": "CTIS" } ], "organization": { "fullName": "Servier", "class": "INDUSTRY" }, "briefTitle": "Phase 1/2 Trial of S241656 in Selected RAS/MAPK Mutation- Positive Malignancies", "officialTitle": "A Phase 1/2, Open-label Study of Oral S241656 (BDTX-4933) as Monotherapy and in Combination With Other Anti-Cancer Therapies in Patients With KRAS, BRAF and Other Selected RAS/MAPK Mutation-Positive Malignancies" }, "statusModule": { "statusVerifiedDate": "2025-10", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2023-04-18", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2028-06", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2028-06", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2023-03-06", "studyFirstSubmitQcDate": "2023-03-15", "studyFirstPostDateStruct": { "date": "2023-03-28", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-10-30", "lastUpdatePostDateStruct": { "date": "2025-11-03", "type": "ESTIMATED" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Institut de Recherches Internationales Servier", "class": "OTHER" } }, "oversightModule": { "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "BDTX-4933-101 is a first-in-human, open-label, Phase 1/2 dose escalation, dose optimization and expansion study designed to evaluate the safety and tolerability of S241656 as monotherapy and in combination with other anti-cancer therapies in participants with selected advanced malignancies. The study population for the Dose Escalation part of the study comprises adults with recurrent advanced/metastatic non-small cell lung cancer (NSCLC), Gastrointestinal (GI) cancers, and other solid tumors harboring KRAS, HRAS, NRAS, BRAF, and/or CRAF (Rapidly Accelerated Fibrosarcoma (RAF1)) mutations or alterations. A dose optimization part in adults with NSCLC may follow the dose escalation phase if the sponsor, in consultation with the safety review committee, decides it is necessary to further characterize the optimal dose. However, the study may also proceed directly to the expansion phase. The study population for the Dose Expansion part of the study comprises adults with advanced/metastatic NSCLC with KRAS and/or BRAF mutations, and with Pancreatic Ductal AdenoCarcinoma (PDAC), ColoRectal Cancer (CRC), and Biliary Tract Cancer (BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations and alterations. All patients will self-administer S241656 orally in 28-day cycles until disease progression, toxicity, withdrawal of consent, or termination of the study." }, "conditionsModule": { "conditions": [ "Non-small Cell Lung Cancer", "Histiocytic Neoplasm", "Histiocytosis", "BRAF Gene Mutation", "BRAF V600E", "BRAF V600 Mutation", "BRAF Mutation-Related Tumors", "BRAF", "Metastatic Lung Non-Small Cell Carcinoma", "Metastatic Lung Cancer", "Recurrent Lung Cancer", "Recurrent Lung Non-Small Cell Carcinoma", "NSCLC", "Solid Tumor", "Solid Carcinoma", "KRAS G12D", "KRAS G12V", "KRAS Mutation-Related Tumors", "NRAS Gene Mutation", "Thyroid Cancer", "Thyroid Carcinoma", "Colorectal Cancer", "Colorectal Carcinoma", "Recurrent Histiocytic and Dendritic Cell Neoplasm", "Brain Metastases", "Recurrent NSCLC", "KRAS G13C", "Acquired Resistance to KRAS G12C Inhibitor", "KRAS G12A", "KRAS G12F", "KRAS G12R", "KRAS G13D" ], "keywords": [ "BRAF Class I", "BRAF Class II", "BRAF Class III", "KRAS", "Intolerant histiocytic neoplasm", "BDTX-4933", "Phase 1", "dose escalation", "dose expansion", "MAPK", "mitogen-activated protein kinase", "RAS", "RAF", "Upstream oncogenic alterations", "RAF inhibitor", "intracranial disease", "CRAF", "NRAS", "RAF fusions" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1", "PHASE2" ], "designInfo": { "allocation": "NON_RANDOMIZED", "interventionModel": "SEQUENTIAL", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 554, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "Part 1A: Dose Escalation NSCLC", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy at escalating dose levels until the biologically effective dose (BED) range is determined.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 1B: Dose Escalation GI Tumors", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 1C: Dose Escalation PDAC", "type": "EXPERIMENTAL", "description": "S241656 will be administered in combination with gemcitabine/nab-paclitaxel at escalating dose levels until the BED range is determined.", "interventionNames": [ "Drug: S241656", "Drug: Gemcitabine", "Drug: Nab-paclitaxel" ] }, { "label": "Part 1D: Dose Escalation CRC", "type": "EXPERIMENTAL", "description": "S241656 will be administered in combination with FOLFOX6/FOLFOX7 or FOLFIRI, and panitumumab or cetuximab at escalating dose levels until the BED range is determined.", "interventionNames": [ "Drug: S241656", "Drug: FOLFOX6/FOLFOX7", "Drug: FOLFIRI", "Drug: Cetuximab", "Drug: Panitumumab" ] }, { "label": "Part 1E: Dose Escalation Other Solid Tumors", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy at escalating dose levels until the BED range is determined.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2A: Dose Optimization NSCLC", "type": "EXPERIMENTAL", "description": "S241656 will be administered to further characterize the optimal dose.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2A1: Dose Expansion NSCLC with KRAS non-G12C mutations", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2A2: Dose Expansion NSCLC with BRAF mutations", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2A3: Dose Expansion NSCLC with KRAS non-G12C or BRAF mutations/alterations", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range. Participants must also have active CNS metastatic disease", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2A4: Dose Expansion NSCLC with a KRAS G12C mutation", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range. Participants must have received and progressed upon G12C targeted therapy", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2B1: Dose Expansion PDAC", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2B2: Dose Expansion CRC", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2B3: Dose Expansion BTC", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy in the BED range.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2C1: Dose Expansion PDAC", "type": "EXPERIMENTAL", "description": "S241656 will be administered in combination with anti-cancer therapies in the BED range. The combination therapies to be used will be determined in the future.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2D1: Dose Expansion CRC", "type": "EXPERIMENTAL", "description": "S241656 will be administered in combination with anti-cancer therapies in the BED range. The combination therapies to be used will be determined in the future.", "interventionNames": [ "Drug: S241656" ] }, { "label": "Part 2F: Exploratory Food Effect", "type": "EXPERIMENTAL", "description": "S241656 will be administered as a monotherapy.", "interventionNames": [ "Drug: S241656" ] } ], "interventions": [ { "type": "DRUG", "name": "S241656", "description": "RAF inhibitor targeting all classes of oncogenic BRAF alterations (Classes I, II, and III) and constitutively active CRAF, KRAS or NRAS mutations", "armGroupLabels": [ "Part 1A: Dose Escalation NSCLC", "Part 1B: Dose Escalation GI Tumors", "Part 1C: Dose Escalation PDAC", "Part 1D: Dose Escalation CRC", "Part 1E: Dose Escalation Other Solid Tumors", "Part 2A1: Dose Expansion NSCLC with KRAS non-G12C mutations", "Part 2A2: Dose Expansion NSCLC with BRAF mutations", "Part 2A3: Dose Expansion NSCLC with KRAS non-G12C or BRAF mutations/alterations", "Part 2A4: Dose Expansion NSCLC with a KRAS G12C mutation", "Part 2A: Dose Optimization NSCLC", "Part 2B1: Dose Expansion PDAC", "Part 2B2: Dose Expansion CRC", "Part 2B3: Dose Expansion BTC", "Part 2C1: Dose Expansion PDAC", "Part 2D1: Dose Expansion CRC", "Part 2F: Exploratory Food Effect" ], "otherNames": [ "BDTX-4933" ] }, { "type": "DRUG", "name": "FOLFOX6/FOLFOX7", "description": "Used as a combination therapy and administered intravenously", "armGroupLabels": [ "Part 1D: Dose Escalation CRC" ] }, { "type": "DRUG", "name": "FOLFIRI", "description": "Used as a combination therapy and administered intravenously", "armGroupLabels": [ "Part 1D: Dose Escalation CRC" ] }, { "type": "DRUG", "name": "Cetuximab", "description": "Used as a combination therapy and administered intravenously", "armGroupLabels": [ "Part 1D: Dose Escalation CRC" ] }, { "type": "DRUG", "name": "Panitumumab", "description": "Used as a combination therapy and administered intravenously", "armGroupLabels": [ "Part 1D: Dose Escalation CRC" ] }, { "type": "DRUG", "name": "Gemcitabine", "description": "Used as a combination therapy and administered intravenously", "armGroupLabels": [ "Part 1C: Dose Escalation PDAC" ] }, { "type": "DRUG", "name": "Nab-paclitaxel", "description": "Used as a combination therapy and administered intravenously", "armGroupLabels": [ "Part 1C: Dose Escalation PDAC" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Dose Escalation: Incidence of dose-limiting toxicities (DLTs)", "description": "A DLT is defined as any event meeting the DLT criteria occurring within the first 28-day cycle", "timeFrame": "The first 28-day cycle (Cycle 1)" }, { "measure": "Dose Escalation: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Optimization/Expansion: Objective response (OR)", "timeFrame": "Through study completion, approximately 5 years" } ], "secondaryOutcomes": [ { "measure": "Dose Escalation/Expansion: Incidence and severity of treatment-emergent adverse events (TEAEs)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Maximum plasma concentration (Cmax) of S241656 and its metabolite S243796", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Time of maximum plasma concentration (Tmax) of S241656 and its metabolite S243796", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Area under the plasma drug concentration-time curve (AUC) of S241656 and its metabolite S243796", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Half-life (t1/2) of S241656 and its metabolite S243796", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation: Objective response (OR)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Disease Control (DC)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Clinical Benefit (CB)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Duration of response (DOR)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Time to response (TTR)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Progression-free Survival (PFS)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Overall survival (OS)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Optimization/Expansion: Number of Adverse Events (AEs) and Serious Adverse Events (SAEs)", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Number of Dose Interruptions", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation/Optimization/Expansion: Number of Dose Reductions", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Escalation: Number of Dose Discontinuations", "timeFrame": "Through study completion, approximately 5 years" }, { "measure": "Dose Optimization/Expansion: Changes in allelic fraction of DNA sequence variants detected in ctDNA from baseline to on-treatment time points", "timeFrame": "Through study completion, approximately 5 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Key Inclusion Criteria:\n\n* Life expectancy of ≥ 12 weeks in the opinion of the investigator.\n* Histologically or cytologically confirmed recurrent locally advanced (unresectable) or metastatic solid tumors with documented RAS or RAF mutations or alterations.\n* Adequate bone marrow and organ function.\n* Recovered from toxicity to prior anti-cancer therapy.\n\nPart 1 Dose Escalation cohort ONLY:\n\n* Part 1A: Advanced/metastatic NSCLC with KRAS non-G12C, HRAS, NRAS, BRAF or CRAF (RAF1) mutations or alterations\n* Part 1B: Advanced/metastatic GI tumors (e.g., PDAC, CRC, and BTC) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations\n* Part 1C: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations\n* Part 1D: Colorectal adenocarcinoma with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations\n* Part 1E: Other advanced/metastatic non-GI, non-NSCLC solid tumors with KRAS, HRAS, NRAS, BRAF, CRAF (RAF1) mutations or alterations\n\nPart 2 Dose Optimization and Expansion cohorts ONLY:\n\n* Part 2A: Advanced/metastatic NSCLC with KRAS non-G12C mutations and/or BRAF mutations\n* Part 2A1: Advanced/metastatic NSCLC with KRAS non-G12C mutations\n* Part 2A2: Advanced/metastatic NSCLC with BRAF mutations\n* Part 2A3: Advanced/metastatic NSCLC with KRAS non-G12C or BRAF mutations or alterations and active CNS metastatic disease\n* Part 2A4: Advanced/metastatic NSCLC with a KRAS G12C mutation\n* Part 2B1: Advanced/metastatic PDAC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations\n* Part 2B2: Advanced/metastatic CRC with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations\n* Part 2B3: Advanced/metastatic BTC (adenocarcinoma) with KRAS, HRAS, NRAS, BRAF, and/or CRAF (RAF1) mutations or alterations\n\nKey Exclusion Criteria:\n\n* Cancer that has a known MEK1/2 mutation.\n* Known allergy/hypersensitivity to excipients of S241656 or to any of the registered IMPs administered in combination.\n* Any contra-indication, to use of any of the combination chemotherapy or anti-EGFR therapy partners administered as part of this trial.\n* Major surgery within 4 weeks of study entry or planned during study.\n* Ongoing anticancer therapy.\n* Ongoing radiation therapy.\n* Uncontrolled or active clinically relevant bacterial, fungal, or specific viral infection requiring systemic therapy.\n* Clinically significant cardiovascular disease.\n* Symptomatic spinal cord compression.\n* Evidence of active malignancy (other than study-specific malignancies) requiring systemic therapy within the next 2 years.\n* History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO.\n* Females who are pregnant or breastfeeding.\n* Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.\n* Prior use of experimental agents that target the KRAS/BRAF/MEK/ERK pathway.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Institut de Recherches Internationales Servier (I.R.I.S.), Clinical Studies Department", "role": "CONTACT", "phone": "+33 1 55 72 60 00", "email": "scientificinformation@servier.com" } ], "locations": [ { "facility": "Banner Health- MD Anderson Cancer Center", "status": "RECRUITING", "city": "Gilbert", "state": "Arizona", "zip": "85234", "country": "United States", "contacts": [ { "name": "Brandi Luzania", "role": "CONTACT", "phone": "480-256-5488", "email": "Brandi.Luzania@bannerhealth.com" }, { "name": "Jiaxin Niu, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 33.35283, "lon": -111.78903 } }, { "facility": "University of Colorado - Aurora Cancer Center", "status": "NOT_YET_RECRUITING", "city": "Aurora", "state": "Colorado", "zip": "80045", "country": "United States", "contacts": [ { "name": "Halle Kuykendall", "role": "CONTACT", "phone": "720-848-0356", "email": "halle.kuykendall@cuanschutz.edu" } ], "geoPoint": { "lat": 39.72943, "lon": -104.83192 } }, { "facility": "Georgetown University Lombardi Cancer Center", "status": "NOT_YET_RECRUITING", "city": "Washington D.C.", "state": "District of Columbia", "zip": "20007", "country": "United States", "contacts": [ { "role": "CONTACT", "phone": "202-444-2223", "email": "Chul.Kim@gunet.georgetown.edu" }, { "name": "Chul Kim, MD", "role": "PRINCIPAL_INVESTIGATOR" } ], "geoPoint": { "lat": 38.89511, "lon": -77.03637 } }, { "facility": "Dana-Farber Cancer Institute", "status": "RECRUITING", "city": "Boston", "state": "Massachusetts", "zip": "02215", "country": "United States", "contacts": [ { "name": "Start Your Patient Journey to Cancer Care and Support", "role": "CONTACT", "phone": "877-442-3324" } ], "geoPoint": { "lat": 42.35843, "lon": -71.05977 } }, { "facility": "South Texas Accelerated Research Therapeutics (START) Midwest", "status": "RECRUITING", "city": "Grand Rapids", "state": "Michigan", "zip": "49546", "country": "United States", "contacts": [ { "name": "Julie Burns", "role": "CONTACT", "phone": "616-954-5559", "email": "julie.burns@startmidwest.com" }, { "name": "Jade Blakeman", "role": "CONTACT", "phone": "616-954-5551", "email": "jade.blakeman@startmidwest.com" } ], "geoPoint": { "lat": 42.96336, "lon": -85.66809 } }, { "facility": "Masonic Cancer Center University of Minnesota", "status": "RECRUITING", "city": "Minneapolis", "state": "Minnesota", "zip": "55455", "country": "United States", "contacts": [ { "name": "Amit Kulkarni, MBBS", "role": "CONTACT", "phone": "612-624-0123", "email": "kulkarni@umn.edu" }, { "name": "Sara Crane", "role": "CONTACT", "email": "crane202@umn.edu" } ], "geoPoint": { "lat": 44.97997, "lon": -93.26384 } }, { "facility": "Washington University", "status": "RECRUITING", "city": "St Louis", "state": "Missouri", "zip": "63130", "country": "United States", "contacts": [ { "name": "Medical Oncology Clinical Call Center", "role": "CONTACT", "phone": "314-747-1171", "email": "MedicalOncologyClinicalCallCenter@dom.wustl.edu" } ], "geoPoint": { "lat": 38.62727, "lon": -90.19789 } }, { "facility": "Memorial Sloan Kettering Cancer Center", "status": "RECRUITING", "city": "New York", "state": "New York", "zip": "10065", "country": "United States", "contacts": [ { "name": "Michael Offin, MD", "role": "CONTACT" }, { "role": "CONTACT", "phone": "646-888-8538" } ], "geoPoint": { "lat": 40.71427, "lon": -74.00597 } }, { "facility": "NEXT Virginia", "status": "RECRUITING", "city": "Fairfax", "state": "Virginia", "zip": "22031", "country": "United States", "contacts": [ { "name": "Blake Patterson", "role": "CONTACT", "phone": "703-783-4505", "email": "bpatterson@nextoncology.com" } ], "geoPoint": { "lat": 38.84622, "lon": -77.30637 } }, { "facility": "Fred Hutchinson Cancer Research Center", "status": "RECRUITING", "city": "Seattle", "state": "Washington", "zip": "98109", "country": "United States", "contacts": [ { "name": "Rebecca Wood", "role": "CONTACT", "phone": "206-606-6970", "email": "rwood1@seattlecca.org" } ], "geoPoint": { "lat": 47.60621, "lon": -122.33207 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D002289", "term": "Carcinoma, Non-Small-Cell Lung" }, { "id": "D015614", "term": "Histiocytosis" }, { "id": "D008175", "term": "Lung Neoplasms" }, { "id": "D013964", "term": "Thyroid Neoplasms" }, { "id": "D015179", "term": "Colorectal Neoplasms" }, { "id": "D001932", "term": "Brain Neoplasms" } ], "ancestors": [ { "id": "D002283", "term": "Carcinoma, Bronchogenic" }, { "id": "D001984", "term": "Bronchial Neoplasms" }, { "id": "D012142", "term": "Respiratory Tract Neoplasms" }, { "id": "D013899", "term": "Thoracic Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D008171", "term": "Lung Diseases" }, { "id": "D012140", "term": "Respiratory Tract Diseases" }, { "id": "D008206", "term": "Lymphatic Diseases" }, { "id": "D006425", "term": "Hemic and Lymphatic Diseases" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D006258", "term": "Head and Neck Neoplasms" }, { "id": "D004700", "term": "Endocrine System Diseases" }, { "id": "D013959", "term": "Thyroid Diseases" }, { "id": "D007414", "term": "Intestinal Neoplasms" }, { "id": "D005770", "term": "Gastrointestinal Neoplasms" }, { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D005767", "term": "Gastrointestinal Diseases" }, { "id": "D003108", "term": "Colonic Diseases" }, { "id": "D007410", "term": "Intestinal Diseases" }, { "id": "D012002", "term": "Rectal Diseases" }, { "id": "D016543", "term": "Central Nervous System Neoplasms" }, { "id": "D009423", "term": "Nervous System Neoplasms" }, { "id": "D001927", "term": "Brain Diseases" }, { "id": "D002493", "term": "Central Nervous System Diseases" }, { "id": "D009422", "term": "Nervous System Diseases" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C480833", "term": "IFL protocol" }, { "id": "D000068818", "term": "Cetuximab" }, { "id": "D000077544", "term": "Panitumumab" }, { "id": "D000093542", "term": "Gemcitabine" }, { "id": "C520255", "term": "130-nm albumin-bound paclitaxel" } ], "ancestors": [ { "id": "D061067", "term": "Antibodies, Monoclonal, Humanized" }, { "id": "D000911", "term": "Antibodies, Monoclonal" }, { "id": "D000906", "term": "Antibodies" }, { "id": "D007136", "term": "Immunoglobulins" }, { "id": "D007162", "term": "Immunoproteins" }, { "id": "D001798", "term": "Blood Proteins" }, { "id": "D011506", "term": "Proteins" }, { "id": "D000602", "term": "Amino Acids, Peptides, and Proteins" }, { "id": "D012712", "term": "Serum Globulins" }, { "id": "D005916", "term": "Globulins" }, { "id": "D006571", "term": "Heterocyclic Compounds" }, { "id": "D003841", "term": "Deoxycytidine" }, { "id": "D003562", "term": "Cytidine" }, { "id": "D011741", "term": "Pyrimidine Nucleosides" }, { "id": "D011743", "term": "Pyrimidines" }, { "id": "D006573", "term": "Heterocyclic Compounds, 1-Ring" } ] } }, "hasResults": false }, { "protocolSection": { "identificationModule": { "nctId": "NCT06411691", "orgStudyIdInfo": { "id": "J2456" }, "secondaryIdInfos": [ { "id": "IRB00427416", "type": "OTHER", "domain": "Johns Hopkins Medicine IRB" }, { "id": "1R01CA296410-01", "type": "NIH", "link": "https://reporter.nih.gov/quickSearch/1R01CA296410-01" }, { "id": "HT94252410948", "type": "OTHER_GRANT", "domain": "Department of Defense" } ], "organization": { "fullName": "Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins", "class": "OTHER" }, "briefTitle": "KRAS-Targeted Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Cancer", "officialTitle": "Pooled Mutant KRAS-Targeted Long Peptide Vaccine Combined With Balstilimab and Botensilimab for Patients With Stage IV MMR-p Colorectal Cancer and Pancreatic Ductal Adenocarcinoma" }, "statusModule": { "statusVerifiedDate": "2025-04", "overallStatus": "RECRUITING", "expandedAccessInfo": { "hasExpandedAccess": false }, "startDateStruct": { "date": "2024-11-04", "type": "ACTUAL" }, "primaryCompletionDateStruct": { "date": "2028-11-01", "type": "ESTIMATED" }, "completionDateStruct": { "date": "2028-11-01", "type": "ESTIMATED" }, "studyFirstSubmitDate": "2024-05-08", "studyFirstSubmitQcDate": "2024-05-08", "studyFirstPostDateStruct": { "date": "2024-05-13", "type": "ACTUAL" }, "lastUpdateSubmitDate": "2025-04-03", "lastUpdatePostDateStruct": { "date": "2025-04-06", "type": "ACTUAL" } }, "sponsorCollaboratorsModule": { "responsibleParty": { "type": "SPONSOR" }, "leadSponsor": { "name": "Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins", "class": "OTHER" }, "collaborators": [ { "name": "Agenus Inc.", "class": "INDUSTRY" }, { "name": "Private Philanthropic Funds", "class": "OTHER" }, { "name": "National Cancer Institute (NCI)", "class": "NIH" }, { "name": "United States Department of Defense", "class": "FED" } ] }, "oversightModule": { "oversightHasDmc": true, "isFdaRegulatedDrug": true, "isFdaRegulatedDevice": false }, "descriptionModule": { "briefSummary": "Phase 1b study evaluating the efficacy and immune response to a synthetic long peptide mutant KRAS vaccine (SPL mKRASvax) combined with Balstilimab and Botensilimab for unresectable or metastatic mismatch repair-proficient (MMR-p) colorectal cancer (mCRC) or unresectable or metastatic MMR-p pancreatic ductal adenocarcinoma (PDAC) patients with measurable disease following first-line chemotherapy." }, "conditionsModule": { "conditions": [ "Colorectal Cancer", "Pancreatic Cancer" ], "keywords": [ "mKRAS peptide vaccines", "Anti-PD-1 (anti-check point inhibitor)", "PD-L1 (check point inhibitor)", "Balstilimab", "Botensilimab", "Cancer Vaccines", "SLP mKRASvax (peptide vaccine + Poly-ICLC (Hiltonol))", "Immunotherapy", "Colon Cancer", "Metastatic colon cancer", "Pancreatic Ductal Adenocarcinoma (PDAC)", "Metastatic pancreatic cancer", "Hiltonol" ] }, "designModule": { "studyType": "INTERVENTIONAL", "phases": [ "PHASE1" ], "designInfo": { "allocation": "NA", "interventionModel": "SINGLE_GROUP", "primaryPurpose": "TREATMENT", "maskingInfo": { "masking": "NONE" } }, "enrollmentInfo": { "count": 54, "type": "ESTIMATED" } }, "armsInterventionsModule": { "armGroups": [ { "label": "SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab", "type": "EXPERIMENTAL", "interventionNames": [ "Drug: KRAS Vaccine with Poly-ICLC adjuvant", "Drug: Balstilimab", "Drug: Botensilimab" ] } ], "interventions": [ { "type": "DRUG", "name": "KRAS Vaccine with Poly-ICLC adjuvant", "description": "SLP mKRASvax with Poly-ICLC adjuvant will be administered on days 1, 8, 15 and 22 in Cycle 1 (Prime Phase) and on day 1 in cycle 4 and every other cycle and beyond (Boost Phase). Up to 5 subcutaneous injections will be administered in the upper thighs, arms and/or back.\n\nDrug: 0.3 mg per peptide vaccine + 0.5mg Poly-ICLC", "armGroupLabels": [ "SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab" ], "otherNames": [ "Hiltonol® (Poly-ICLC)" ] }, { "type": "DRUG", "name": "Balstilimab", "description": "240 mg will be administered as a 30 minute IV. Infusion (-10/+25 minutes) on day 1 and day 15 during Cycle 1 in Prime Phase and on day 1 and day 15 of every cycle in the Boost Phase beginning on Cycle 2 (for a maximum of 2 years from initial vaccination).\n\nDrug: 240 mg IV", "armGroupLabels": [ "SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab" ], "otherNames": [ "AGEN2034" ] }, { "type": "DRUG", "name": "Botensilimab", "description": "75 mg will be administered as a 30 minute IV. Infusion (-10/+25 minutes) on Cycle 1 day 1 in Prime Phase and on Cycle 2 day 15 in the Boost Phase.\n\nDrug: 75 mg IV", "armGroupLabels": [ "SLP mKRASvax (Up to 1.8mg peptide + 0.5 mg Poly-ICLC (Hiltonol), Botensilimab and Balstilimab" ], "otherNames": [ "AGEN1181" ] } ] }, "outcomesModule": { "primaryOutcomes": [ { "measure": "Cohort A: Progression-free Survival (PFS) for maintenance mPDAC cohort", "description": "PFS is defined as the number of mPDAC patients free of progression at 4 months since the initiation of therapy - disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30percent decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20percent increase in sum of diameters of target lesions, Stable Disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.", "timeFrame": "4 months" }, { "measure": "Cohort B: Objective Response Rate (ORR) for maintenance mCRC cohort", "description": "ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.", "timeFrame": "3 years" }, { "measure": "Cohort C: Objective Response Rate (ORR) for KRAS-inhibitor exposed mPDAC cohort", "description": "ORR is defined as the number of mCRC patients who are administered at least 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30percent decrease in sum of diameters of target lesions, progressive disease (PD) is \>20percent increase in sum of diameters of target lesions, stable disease (SD) is \<30percent decrease or \<20percent increase in sum of diameters of target lesions.", "timeFrame": "3 years" }, { "measure": "Number of participants experiencing study drug-related toxicities", "description": "Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0", "timeFrame": "3 years" } ], "secondaryOutcomes": [ { "measure": "Objective Response Rate (ORR) per RECIST 1.1", "description": "ORR is defined as the number of mPDAC patients who are administered at least 1 dose of SLP mKRASvax and balstilimab +/- botensilimab achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on the Kaplan-Meier curve.", "timeFrame": "3 years" }, { "measure": "Disease Control Rate (DCR)", "description": "DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 2 months post first vaccination. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.", "timeFrame": "2 months" }, { "measure": "Disease Control Rate (DCR)", "description": "DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 6 months post first vaccination. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.", "timeFrame": "6 months" }, { "measure": "Disease Control Rate (DCR)", "description": "DCR is defined as the number of patients who are administered ≥ 1 dose of SLP mKRASvax achieving a complete response (CR) or partial response (PR) and stable disease (SD) based on the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) at 12 months post first vaccination. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.", "timeFrame": "12 months" }, { "measure": "Progression-free Survival (PFS) per RECIST 1.1", "description": "PFS is defined as the time from cycle 1, day 1 of KRAS vaccine and balstilimab and botensilimab until first documented local disease progression (progressive disease \[PD\] or relapse from complete response \[CR\] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =\>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is \>20% increase in sum of diameters of target lesions, Stable Disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions.", "timeFrame": "3 years" } ] }, "eligibilityModule": { "eligibilityCriteria": "Inclusion Criteria:\n\n* Age ≥18 years.\n* Have histologically or cytologically - proven cancer of the pancreas or colon.\n* Have tumor lesions amenable to repeated biopsy, and patient's acceptance to have a tumor biopsy of an accessible lesion at baseline and on treatment if the lesion can be biopsied with acceptable clinical risk (as judged by the investigator).\n* Measurable disease as per RECIST 1.1.\n* Have sufficient and accessible tissue for next generation sequencing (NGS) and immune-phenotyping.\n* Have one of the KRAS mutations included in the vaccine at the time of vaccination expressed in tumor.\n* Cohort A: Have received 4-6 months of FOLFIRINOX or gemcitabine+nab-paclitaxel for the 1st line treatment of metastatic unresectable PDAC.\n* Cohort B: Have received 4-6 months of 1st line SOC chemotherapy per NCCN guidelines (FOLFIRINOX, FOLFOX, FOLFIRI +/- targeted therapy with VEGFi or EGFRi) of metastatic CRC.\n* Cohort C: Have received no more than 3 lines of systemic chemotherapy, including prior KRAS inhibitor.\n* Eastern Cooperative Oncology Group (ECOG) performance status 0.\n* Life expectancy of greater than 3 months.\n* Patients must have adequate organ and marrow function defined by study-specified laboratory tests prior to initial study drug.\n* Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.\n* Men must use acceptable form of birth control while on study.\n* Ability to understand and willingness to sign a written informed consent document.\n\nExclusion Criteria:\n\n* Is a candidate for definitive surgical resection.\n* Known history or evidence of brain metastases and/or leptomeningeal spread.\n* Prior treatment with immunotherapy agents (including, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, etc.).\n* Receiving active immunosuppressive agents or chronic use of systemic corticosteroids within 14 days of vaccine treatment.\n* Has active autoimmune disease that has required systemic treatment in the past 5 years, or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.\n* Known history or concurrent interstitial lung disease.\n* Has a pulse oximetry \< 95% on room air.\n* Requires the use of home oxygen.\n* Infection with HIV or hepatitis B or C.\n* Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.\n* Has been diagnosed with another cancer or myeloproliferative disorder in the past 5 years except for superficial bladder cancer, non-melanoma skin cancers, DCIS, a low-grade prostate cancer, or a cancer not expected to impact life expectancy and not requiring therapy.\n* Has had surgery within 28 days of dosing of investigational agent, excluding minor procedures (dental work, skin biopsy, etc.), celiac plexus block, and biliary stent placement.\n* Has received any non-oncology live vaccine therapy used for prevention of infectious diseases within 28 days of study treatment.\n* If at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs or other substance abuse (including alcohol) that could potentially interfere with adherence to study procedures or requirements.\n* Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.\n* Unwilling or unable to follow the study schedule for any reason.\n* Are pregnant or breastfeeding.\n* Any radiological or clinical pleural effusions or ascites.\n* History of malignant small bowel obstruction.\n* On parenteral nutrition.\n* Known or suspected hypersensitivity to Hiltonol.", "healthyVolunteers": false, "sex": "ALL", "minimumAge": "18 Years", "stdAges": [ "ADULT", "OLDER_ADULT" ] }, "contactsLocationsModule": { "centralContacts": [ { "name": "Colleen Apostol, RN", "role": "CONTACT", "phone": "410-614-3644", "email": "GIClinicalTrials@jhmi.edu" }, { "name": "Joann Santmyer, RN", "role": "CONTACT", "phone": "410-614-3644", "email": "GIClinicalTrials@jhmi.edu" } ], "overallOfficials": [ { "name": "Nilofer Azad, MD", "affiliation": "SKCCC Johns Hopkins Medical Institution", "role": "PRINCIPAL_INVESTIGATOR" } ], "locations": [ { "facility": "Sidney Kimmel Comprehensive Cancer Center", "status": "RECRUITING", "city": "Baltimore", "state": "Maryland", "zip": "21231", "country": "United States", "contacts": [ { "name": "Colleen Apostol, RN", "role": "CONTACT", "phone": "410-614-3644", "email": "GIClinicalTrials@jhmi.edu" }, { "name": "Joann Santmyer, RN", "role": "CONTACT", "phone": "410-614-3644", "email": "GIClinicalTrials@jhmi.edu" } ], "geoPoint": { "lat": 39.29038, "lon": -76.61219 } } ] }, "ipdSharingStatementModule": { "ipdSharing": "NO" } }, "derivedSection": { "miscInfoModule": { "versionHolder": "2025-11-14" }, "conditionBrowseModule": { "meshes": [ { "id": "D015179", "term": "Colorectal Neoplasms" }, { "id": "D010190", "term": "Pancreatic Neoplasms" }, { "id": "D003110", "term": "Colonic Neoplasms" } ], "ancestors": [ { "id": "D007414", "term": "Intestinal Neoplasms" }, { "id": "D005770", "term": "Gastrointestinal Neoplasms" }, { "id": "D004067", "term": "Digestive System Neoplasms" }, { "id": "D009371", "term": "Neoplasms by Site" }, { "id": "D009369", "term": "Neoplasms" }, { "id": "D004066", "term": "Digestive System Diseases" }, { "id": "D005767", "term": "Gastrointestinal Diseases" }, { "id": "D003108", "term": "Colonic Diseases" }, { "id": "D007410", "term": "Intestinal Diseases" }, { "id": "D012002", "term": "Rectal Diseases" }, { "id": "D004701", "term": "Endocrine Gland Neoplasms" }, { "id": "D010182", "term": "Pancreatic Diseases" }, { "id": "D004700", "term": "Endocrine System Diseases" } ] }, "interventionBrowseModule": { "meshes": [ { "id": "C019531", "term": "poly ICLC" }, { "id": "C000720935", "term": "balstilimab" } ] } }, "hasResults": false } ], "nextPageToken": "ZVNj7o2Elu8o3lptRcizoKb-mpOQJJxpYfet2_cW" }