FOENIX-CCA2
Regimen
- Experimental
- Futibatinib 20 mg PO QD (continuous, no off-week schedule) — irreversible (covalent) FGFR1-4 inhibitor, distinct mechanism from pemigatinib (reversible)
- Control
- single-arm / no comparator
Population
Previously treated (≥1 prior systemic therapy) unresectable or metastatic ICC with FGFR2 fusions or other rearrangements by central next-generation sequencing (FoundationOne CDx). 100% ICC by design (FGFR2 rearrangements are ICC-exclusive). 67% had ≥2 prior lines.
Key finding
Futibatinib received FDA accelerated approval in September 2022 for previously treated FGFR2-rearranged ICC, making it the second FGFR2-targeted therapy approved for CCA. The covalent (irreversible) binding mechanism was hypothesized to overcome certain acquired resistance mutations that arise on reversible inhibitors like pemigatinib. ORR 41.7% is numerically higher than FIGHT-202 Cohort A (35.5%), though cross-trial comparison is confounded by patient selection and testing platform differences. Both trials validated FGFR2 rearrangement (not just amplification) as the actionable molecular event.
Source: PMID 36652354
Timeline
Guideline citations
- NCCN BTC (p.35)