Phase 2a pemigatinib FGFR1/2/3 inhibitor alternated with durvalumab PD‑L1 blockade

This Ohio State University Comprehensive Cancer Center Phase 2a study tests a “cyclical/alternating” first-line strategy for unresectable, locally advanced, or metastatic biliary tract cancers (commonly intrahepatic cholangiocarcinoma) with FGFR2 alterations. Patients receive blocks of gemcitabine (a nucleoside analog that inhibits DNA synthesis) plus cisplatin (a platinum DNA–crosslinking agent) with durvalumab (AstraZeneca’s anti–PD‑L1 monoclonal antibody), alternating with pemigatinib (Incyte’s oral FGFR1/2/3 tyrosine kinase inhibitor). The aim is to see whether alternating targeted FGFR suppression with chemo-immunotherapy can deepen and prolong disease control while potentially limiting continuous selective pressure that can drive FGFR resistance. FGFR2 fusions/rearrangements are a defining, targetable subgroup in intrahepatic cholangiocarcinoma (~10–15%), and pemigatinib is already established in later-line FGFR2-altered disease, making the key commercial/scientific angle the move into the first-line setting. Today’s care for newly diagnosed advanced biliary tract cancer is gemcitabine/cisplatin plus durvalumab, with FGFR inhibitors typically used after progression in FGFR2-positive cases.