TY - JOUR
T1 - Futibatinib, an Irreversible FGFR1–4 Inhibitor, in Patients with Advanced Solid Tumors Harboring FGF/FGFR Aberrations
T2 - A Phase I Dose-Expansion Study
AU - Meric-Bernstam, Funda
AU - Bahleda, Rastislav
AU - Hierro, Cinta
AU - Sanson, Marc
AU - Bridgewater, John
AU - Arkenau, Hendrik Tobias
AU - Tran, Ben
AU - Kelley, Robin Kate
AU - Park, Joon Oh
AU - Javle, Milind
AU - He, Yaohua
AU - Benhadji, Karim A.
AU - Goyal, Lipika
N1 - Publisher Copyright:
© 2021 The Authors; Published by the American Association for Cancer Research.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122181401&partnerID=8YFLogxK
U2 - 10.1158/2159-8290.CD-21-0697
DO - 10.1158/2159-8290.CD-21-0697
M3 - Article
C2 - 34551969
AN - SCOPUS:85122181401
SN - 2159-8274
VL - 12
SP - 402
EP - 415
JO - Cancer Discovery
JF - Cancer Discovery
IS - 2
ER -