TRIDENT-1

NCT03093116 📎

Regimen

Experimental
Repotrectinib 160 mg PO QD for 14 days then 160 mg BID (continuous) — next-generation TRK inhibitor with activity against resistance mutations (NTRK G595R, G667C, F589L)
Control
single-arm / no comparator

Population

NTRK fusion-positive advanced solid tumors in both TRK inhibitor-naive and TRK inhibitor-pretreated patients; pan-tumor design (Besse B, Nat Med 2026). BTC/CCA subgroup: small, not separately quantified in primary publication due to low NTRK prevalence in BTC (<1%). Designed to address resistance emerging after larotrectinib/entrectinib therapy.

Key finding

Repotrectinib (Augtyro, BMS) received FDA approval in November 2023 for NTRK fusion-positive solid tumors, including both TRK-inhibitor-naive and -pretreated patients. Its compact macrocyclic structure enables accommodation of resistance mutations that arise on first-generation TRK inhibitors (notably NTRK G595R solvent-front mutation), providing a sequential treatment option. For BTC patients progressing on larotrectinib/entrectinib with NTRK resistance mutations, repotrectinib is the designated next-line precision option. Note: PMID 41639379 (Nat Med 2026) is a later updated analysis; initial FDA registration was based on earlier data.

Source: PMID 41639379

Timeline

    Guideline citations

    • NCCN BTC (p.6)