Pemigatinib (FGFR1–3 inhibitor) improves PFS and ORR vs Gem/Cis in 1L FGFR2-rearranged mCCA (FIGHT-302)

Pemigatinib is an oral selective FGFR1–3 tyrosine kinase inhibitor evaluated as first-line therapy in the randomized global Phase 3 FIGHT-302 trial (NCT03656536) in previously untreated unresectable/metastatic cholangiocarcinoma with FGFR2 rearrangement (n=167; study closed early for slow accrual after prescreening >4000 patients). Pemigatinib improved median PFS to 8.3 vs 6.8 months with gemcitabine/cisplatin (HR 0.58, nominal p=.0078) and increased ORR to 47% vs 15.5% with longer median DOR (14.2 vs 6.3 months), but median OS was similar (24.4 vs 25.0 months) and is difficult to interpret given permitted crossover (42 patients received 2L pemigatinib; 2L mPFS 8.1 months); grade ≥3 TEAEs were higher with pemigatinib (78% vs 67%) with similar treatment-related TEAE rates (96% both arms) and fewer discontinuations (6% vs 11%). Versus today’s common 1L SOC of gem/cis + durvalumab in unselected biliary tract cancer (TOPAZ-1; mPFS and OS gains are modest and ORR is typically in the ~20–30% range), FIGHT-302 suggests better tumor shrinkage in this biomarker-enriched subset, but does not yet show an OS advantage in a crossover-permitted design.