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Clinical Trial Matching - Examples

Example 1: NSCLC with EGFR L858R

User Query: "Find clinical trials for Stage IV non-small cell lung cancer with EGFR L858R mutation, failed platinum chemotherapy, ECOG 0-1"

Skill Execution:

Phase 1: Patient Profile Standardization

  • Disease: "non-small cell lung cancer" -> EFO_0003060 (non-small cell lung carcinoma)
  • Gene: EGFR -> Ensembl: ENSG00000146648, Entrez: 1956
  • Biomarker: EGFR L858R -> type: mutation, gene: EGFR, alteration: L858R
  • FDA Biomarker: EGFR is FDA-recognized biomarker (afatinib, osimertinib, erlotinib, gefitinib)

Phase 2: Trial Discovery

  • Disease search: ~200+ trials for NSCLC
  • Biomarker search: "EGFR L858R" -> 10-30 targeted trials
  • Intervention search: "osimertinib" for NSCLC -> 20+ trials
  • Combined and deduplicated: ~50-80 unique candidate trials

Phase 3-6: Analysis

  • Parse eligibility criteria for EGFR L858R requirements
  • Check drug mechanisms for EGFR inhibitors
  • Cross-reference FDA approvals (osimertinib for EGFR L858R NSCLC)
  • Score molecular match: 40/40 for trials requiring EGFR L858R

Expected Top Matches

Trials testing:

  • EGFR TKIs (osimertinib, amivantamab-vmjw)
  • EGFR TKI combinations (TKI + chemotherapy)
  • Next-generation EGFR inhibitors
  • EGFR-targeted ADCs or bispecific antibodies

Example 2: Melanoma with BRAF V600E

User Query: "Patient has BRAF V600E melanoma, failed ipilimumab, looking for trials"

Skill Execution:

Phase 1: Standardization

  • Disease: melanoma -> EFO_0000756
  • Gene: BRAF -> ENSG00000157764, CIViC ID: 5
  • Biomarker: BRAF V600E -> type: mutation
  • FDA: BRAF is FDA-recognized (dabrafenib, vemurafenib, encorafenib)

Phase 2: Trial Discovery

  • "melanoma BRAF V600E" -> BRAF-targeted trials
  • "melanoma immunotherapy" -> post-ipilimumab options
  • Combined targeted + immunotherapy options

Expected Top Matches

  • BRAF/MEK inhibitor combinations (dabrafenib + trametinib)
  • Novel BRAF inhibitors
  • Combination of BRAF inhibition + immunotherapy
  • Anti-PD-1 after ipilimumab
  • Novel immunotherapy combinations

Example 3: Colorectal Cancer with KRAS G12C

User Query: "KRAS G12C colorectal cancer, Stage IV, failed FOLFOX + bevacizumab, microsatellite stable"

Skill Execution:

Phase 1: Standardization

  • Disease: colorectal cancer -> EFO_0005842
  • Gene: KRAS -> ENSG00000133703, CIViC ID: 30
  • Biomarkers: KRAS G12C (mutation), MSS (status)
  • FDA: KRAS G12C targeted (sotorasib approved for NSCLC, under investigation for CRC)

Phase 2: Trial Discovery

  • "colorectal cancer KRAS G12C" -> specific trials
  • "KRAS G12C" without disease filter -> cross-tumor trials
  • "sotorasib" or "adagrasib" for CRC

Expected Top Matches

  • KRAS G12C inhibitor trials (sotorasib, adagrasib) for CRC
  • KRAS G12C + anti-EGFR combinations
  • Novel KRAS inhibitors
  • Basket trials for KRAS G12C any solid tumor

Example 4: Breast Cancer with HER2+

User Query: "HER2-positive breast cancer, failed trastuzumab + pertuzumab, brain metastases"

Skill Execution:

Phase 1: Standardization

  • Disease: breast cancer -> EFO_0000305
  • Gene: HER2/ERBB2 -> ENSG00000141736, CIViC ID: 20
  • Biomarker: HER2 amplification
  • FDA: HER2 recognized (trastuzumab, pertuzumab, T-DXd, tucatinib)

Phase 2: Trial Discovery

  • "breast cancer HER2" + "brain metastases"
  • "trastuzumab deruxtecan" (T-DXd) trials
  • "tucatinib" trials (CNS-penetrant)
  • Post-pertuzumab HER2+ trials

Special Considerations

  • Brain metastases eligibility (many trials exclude CNS disease)
  • CNS-active agents prioritized (tucatinib, T-DXd)

Example 5: NTRK Fusion (Basket Trial)

User Query: "Find trials for NTRK1 fusion, any solid tumor type"

Skill Execution:

Phase 1: Standardization

  • Gene: NTRK1 -> ENSG00000198400, CIViC ID: 197
  • Biomarker: NTRK1 fusion
  • FDA: NTRK recognized (larotrectinib, entrectinib - tissue-agnostic)

Phase 2: Trial Discovery

  • "NTRK fusion" + "basket" or "tumor agnostic"
  • "larotrectinib" and "entrectinib" trials
  • "NTRK" across all cancer types

Expected Top Matches

  • Larotrectinib/entrectinib expansion studies
  • Next-generation TRK inhibitors (selitrectinib, repotrectinib)
  • Basket trials requiring NTRK fusion
  • Combination approaches with TRK inhibition

Example 6: Geographic Search

User Query: "Find Phase II or III lung cancer trials near Boston"

Skill Execution:

Phase 1: Standardization

  • Disease: lung cancer -> EFO_0001071
  • Geographic preference: Boston, Massachusetts

Phase 2: Trial Discovery

  • "lung cancer" Phase II/III
  • Filter by Massachusetts locations

Phase 3: Location Analysis

  • Sites in Massachusetts: Dana-Farber, Massachusetts General, Beth Israel
  • Nearby states: Connecticut, Rhode Island, New Hampshire

Scoring

  • Geographic feasibility weighted more heavily
  • Massachusetts sites: 5/5 points
  • Nearby New England sites: 3/5 points

Output Format

Each example produces a comprehensive markdown report saved to a file with the following key sections:

  1. Executive Summary with top 3 trials and scores
  2. Patient Profile with standardized identifiers
  3. Ranked Trial List with scoring breakdown
  4. Trial Categories (targeted, immunotherapy, combination, basket)
  5. Alternative Options (expanded access, off-label)
  6. Evidence Grading and completeness checklist