1198TiP A phase Ib/II open-label, nonrandomized study of FGFR inhibitor futibatinib in combination with MEK inhibitor binimetinib in patients with advanced KRAS-mutant cancer

Abstract

Treatment options for patients (pts) with KRAS-mutant (KRASmt) cancer, including non–small cell lung cancer (NSCLC), are limited. Combination of MEK inhibitors (MEKi) plus futibatinib had synergistic antitumor activity in different KRASmt NSCLC cell lines. An open-label, nonrandomized phase 1b/2 study (NCT04965818) is being conducted to assess the safety and preliminary antitumor activity of futibatinib plus MEKi binimetinib in pts with KRASmt advanced NSCLC. This phase 1b/2 study contains 2 parts. In the phase Ib dose escalation part, the recommended phase II dose (RP2D) and regimen of futibatinib plus binimetinib in pts with advanced cancer (part 1) will be determined. In the phase II part, pts with KRASmt advanced NSCLC will be enrolled in a cohort of 18 pts to evaluate the preliminary antitumor activity of futibatinib plus binimetinib at the RP2D and regimen (part 2). Pts eligible for part 1 may have any type of advanced cancer for which no other treatment options are available. Pts with KRASmt advanced NSCLC in part 2 must have their KRAS mutation determined by local results from a tumor tissue specimen and have had disease progression on prior standard of care therapy including anti–PD-(L)1 therapy and platinum-based chemotherapy. Key exclusion criteria include any history of known phosphate homeostasis disorder and current evidence of any clinically significant retinal or corneal disorder and any history of retinal vein occlusion. The primary objective is to determine an RP2D based on safety, preliminary activity, and PK/PD results (part 1) and to assess the preliminary antitumor activity of the combination in pts with KRASmt advanced NSCLC based on objective response rate by RECIST 1.1 (part 2). Secondary endpoints include pharmacokinetic parameters, duration of response, disease control rate at 24 weeks, and progression-free survival. Exploratory objectives include correlative analysis to explore biomarkers related to tumor biology and their potential associations with antitumor activity and resistance to the study medications (including circulating tumor DNA). The study was initiated September 2021 and is ongoing. NCT04965818. Professional medical writing and editorial assistance were provided by Tracy Diaz, PhD, and Jennifer Robertson, PhD, at Ashfield MedComms, an Ashfield Health company, and funded by Taiho Oncology, Inc. Taiho Oncology, Inc.