Futibatinib, an Irreversible FGFR1-4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations: A Phase I Dose-Expansion Study

Meric-Bernstam, F; Bahleda, R; Hierro, C; Sanson, M; Bridgewater, J; Arkenau, HT; Tran, B; Kelley, RK; Park, JO; Javle, M; He, Y; Benhadji, KA; Goyal, L

Author(s): Meric-Bernstam, F; Bahleda, R; Hierro, C; Sanson, M; Bridgewater, J; Arkenau, HT; Tran, B; Kelley, RK; Park, JO; Javle, M; He, Y; Benhadji, KA; Goyal, L;
Details: Publication Year 2022-02,Volume 12,Issue #2,Page 402-415
Journal Title: Cancer Discovery
Publication Type: Research article
Abstract: Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, was evaluated in a large multihistology phase I dose-expansion trial that enrolled 197 patients with advanced solid tumors. Futibatinib demonstrated an objective response rate (ORR) of 13.7%, with responses in a broad spectrum of tumors (cholangiocarcinoma and gastric, urothelial, central nervous system, head and neck, and breast cancer) bearing both known and previously uncharacterized FGFR1-3 aberrations. The greatest activity was observed in FGFR2 fusion/rearrangement-positive intrahepatic cholangiocarcinoma (ORR, 25.4%). Some patients with acquired resistance to a prior FGFR inhibitor also experienced responses with futibatinib. Futibatinib demonstrated a manageable safety profile. The most common treatment-emergent adverse events were hyperphosphatemia (81.2%), diarrhea (33.5%), and nausea (30.4%). These results formed the basis for ongoing futibatinib phase II/III trials and demonstrate the potential of genomically selected early-phase trials to help identify molecular subsets likely to benefit from targeted therapy. SIGNIFICANCE: This phase I dose-expansion trial demonstrated clinical activity and tolerability of the irreversible FGFR1-4 inhibitor futibatinib across a broad spectrum of FGFR-aberrant tumors. These results formed the rationale for ongoing phase II/III futibatinib trials in cholangiocarcinoma, breast cancer, gastroesophageal cancer, and a genomically selected disease-agnostic population.This article is highlighted in the In This Issue feature, p. 275.
Keywords: Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use; Bile Duct Neoplasms/*drug therapy/mortality; Cholangiocarcinoma/*drug therapy/mortality; Disease-Free Survival; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Pyrazoles/administration & dosage/adverse effects/*therapeutic use; Pyrimidines/administration & dosage/adverse effects/*therapeutic use; Pyrroles/administration & dosage/adverse effects/*therapeutic use; Receptor, Fibroblast Growth Factor, Type 1/antagonists & inhibitors/*genetics
Department(s): Medical Oncology
PubMed ID: 34551969
Publisher's Version: https://doi.org/10.1158/2159-8290.CD-21-0697
Open Access at Publisher's Site: https://doi.org/10.1158/2159-8290.Cd-21-0697
Terms of Use/Rights Notice: Refer to copyright notice on published article.

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