Phase 1b/2 study to evaluate the FGFRi futibatinib in combination with the MEKi binimetinib in patients with advanced KRASmt tumors.
This is an open-label, nonrandomized, uncontrolled Phase 1b/2 study to determine the recommended phase 2 dose (RP2D) of futibatinib in combination with binimetinib and to explore the preliminary antitumor activity of futibatinib in combination with binimetinib in patients with advanced KRASmt tumors. The study will consist of two parts: * Part 1: Dose-Escalation part to determine the RP2D and dosing schedule of futibatinib in combination with binimetinib in patients with advanced cancer disease * Part 2: Dose-Expansion part to evaluate the preliminary antitumor activity of futibatinib in combination with binimetinib at the RP2D in patients with advanced KRASmt NSCLC Patients will receive study treatment until progressive disease or any other discontinuation or withdrawal criterion is met. No patients were enrolled in Phase 2 as the Sponsor decided to not proceed with the dose expansion Phase 2 part of the TAS-120-204 study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
38
Patients will receive futibatinib once daily in combination with binimetinib twice daily by oral administration on a 21-day cycle
University of California Los Angeles UCLA Cancer
Santa Monica, California, United States
Community Cancer Center North
Indianapolis, Indiana, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Recommended Phase 2 Dose (RP2D) in Part 1
Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities
Time frame: 12 months
Objective Response Rate (ORR) in Part 2
proportion of patients who have achieved a PR or complete response (CR) according to RECIST 1.1.
Time frame: approximately 24 months
Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032
Plasma concentrations of futibatinib, binimetinib, and AR00426032
Time frame: approximately 24 months
PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032
Plasma concentrations of futibatinib, binimetinib, and AR00426032
Time frame: approximately 24 months
PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032
Plasma concentrations of futibatinib, binimetinib, and AR00426032
Time frame: approximately 24 months
PK: Terminal elimination half-life (T1/2) of futibatinib, binimetinib, and AR00426032
Plasma concentrations of futibatinib, binimetinib, and AR00426032
Time frame: approximately 24 months
PK: Minimum plasma concentration before administration (Cmin) of futibatinib, binimetinib, and AR00426032
Plasma concentrations of futibatinib, binimetinib, and AR00426032
Time frame: approximately 24 months
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PK: Accumulation ratio of Cmax and AUC (R) of futibatinib, binimetinib, and AR00426032
Plasma concentrations of futibatinib, binimetinib, and AR00426032
Time frame: approximately 24 months
Duration of response (DOR)
DOR is defined as the length of time between first response and the date of objectively documented progression of disease or death
Time frame: approximately 24 months
Progression-free survival (PFS)
PFS is defined as the time from date of first dose to objectively documented progression of disease or death
Time frame: approximately 24 months
Disease control rate (DCR) at 24 months
DCR is defined as the percentage of patients who have achieved a CR, PR, or SD.
Time frame: approximately 24 months
Number of patients with treatment-emergent adverse events as assessed by CTCAE v5.0
Evaluate safety and tolerability of futibatinib in combination with binimetinib based on treatment-emergent adverse events per CTCAE v5.0(including serious adverse events),clinical laboratory parameters, ECGs, and vital signs
Time frame: Approximately 24 months