NAVIGATE-LAROTRECTINIB

NCT02122913 📎

Regimen

Experimental
Larotrectinib 100 mg PO BID (continuous) — selective pan-TRK inhibitor (NTRK1/2/3)
Control
single-arm / no comparator

Population

TRK (NTRK1/2/3) fusion-positive advanced solid tumors; pan-cancer pooled analysis of 3 trials. BTC/CCA cohort: small (n=2-3 of 55 in primary publication); subsequent expanded analyses report BTC patients. NTRK fusions occur in <1% of all BTC. TRK fusions detected by RNA-based NGS (preferred) or DNA-based fusion panels. Drilon A, NEJM 2018 is the pivotal FDA-registration paper.

Key finding

Larotrectinib received the first-ever tumor-agnostic FDA approval (November 2018) based on NTRK fusion biomarker regardless of tumor histology — a landmark regulatory precedent. The 75% overall ORR is exceptional, driven by pediatric tumors with high NTRK fusion rates; BTC patients respond when NTRK fusions are present, though NTRK fusion prevalence in BTC is <1%, making BTC-specific outcome data sparse in published cohorts. The histology-independent approval was enabled by the mechanistic (driver fusion) argument and the consistency of response across tumor types.

Source: PMID 29466156

Timeline

    Guideline citations

    • NCCN BTC (p.6)