KRYSTAL-1-BTC

NCT03785249 📎

Regimen

Experimental
Adagrasib 600 mg PO BID (continuous) — selective, irreversible KRAS G12C inhibitor (MRTX849)
Control
single-arm / no comparator

Population

KRAS G12C-mutated advanced solid tumors excluding NSCLC and CRC (those had dedicated KRYSTAL-1 cohorts); pan-tumor basket. BTC/CCA cohort: n=12 of 112 pan-tumor non-NSCLC/CRC patients (Bekaii-Saab TS, JCO 2023). KRAS G12C mutation occurs in ~1-2% BTC, predominantly ICC. KRAS G12C detected by local or central solid tumor NGS panel.

Key finding

Adagrasib demonstrated anti-tumor activity in KRAS G12C-mutated BTC (ORR 33.3%, n=12), providing proof-of-concept for KRAS G12C targeting in this disease. BTC was the first GI tumor type beyond NSCLC/CRC where KRAS G12C targeting showed activity. The small BTC N (n=12) produces wide confidence intervals but the disease control rate of 83.3% signals meaningful biological activity. Adagrasib received FDA accelerated approval for KRAS G12C-mutated solid tumors (June 2024, tumor-agnostic). Combination strategies (adagrasib + cetuximab, or with SOS1 inhibitors) are being explored to enhance efficacy in KRAS G12C tumors.

Source: PMID 37099736

Timeline

    Guideline citations

    • NCCN BTC (p.79)