pemigatinib

Overview

Pemigatinib is a selective, reversible inhibitor of FGFR1/2/3, developed for FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (iCCA). It targets the FGFR2 kinase and received FDA accelerated approval for previously treated FGFR2 fusion/rearrangement-positive iCCA based on the FIGHT-202 phase II trial.

Evidence in the corpus

  • FGFR2 fusion/rearrangement-positive iCCA: FIGHT-202 phase II ORR 35.5%, mPFS 6.9 mo, mOS 21.1 mo; positioned as second-line targeted therapy after gemcitabine + cisplatin failure in cholangiocarcinoma (IHCH/EHCH/CHOL); secondary on-target FGFR2 kinase-domain resistance mutations (N550, V565) emerge in ~60% of patients on reversible inhibitors PMID:25526346

Resistance mechanisms

  • Secondary FGFR2 kinase-domain mutations at N550 and V565 emerge in ~60% of patients on reversible FGFR inhibitors including pemigatinib; covalent inhibitor futibatinib retains activity against these variants PMID:25526346
  • CDKN2A/CDKN2B deletion emerges as an acquired-resistance mechanism in FGFR2 fusion-positive iCCA after FGFR inhibitor therapy PMID:25526346
  • Wild-type EGFR bypass signaling contributes to FGFR-inhibitor resistance; co-inhibition of EGFR enhances FGFR-inhibitor response in preclinical models PMID:25526346

Cancer types (linked)

Sources

This page was processed by crosslinker on 2026-05-14.