Phase 1b/2 Study of Futibatinib in Combination With Binimetinib in Patients With Advanced KRAS Mutant Cancer

Phase 1

Terminated

• Conditions: KRAS Gene Mutation; Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations; Non-Small Cell Lung Cancer
• Interventions: Drug: Futibatinib and Binimetinib

• Registration Number: NCT04965818
• Lead Sponsor: Taiho Oncology, Inc.

Brief Summary

Phase 1b/2 study to evaluate the FGFRi futibatinib in combination with the MEKi binimetinib in patients with advanced KRASmt tumors.

Detailed Description

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.

Study Timeline

• Study First Submitted: 2021-07-06
• Study First Submitted QC: 2021-07-14
• Study First Posted: 2021-07-16
• Study Start: 2021-09-20
• Primary Completion: 2023-06-11
• Study Completion: 2023-09-21
• Status Verified: 2023-10
• Last Update Submitted: 2024-06-25
• Last Update Posted: 2024-06-27

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 38

Inclusion Criteria

• Histologically confirmed advanced cancer of any tumor type (Part 1) or NSCLC with a confirmed KRAS mutation as determined by local results (Part 2)
• Appropriate candidate for experimental therapy
• For patients in Part 2 only: Patient has radiographically measurable disease per RECIST 1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Adequate cardiac function (Left ventricular ejection fraction (LVEF) ≥50% )
• Adequate organ function
• Must have tumor tissue specimen available (optional for patients in Part 1)

Exclusion Criteria

• History or current evidence of calcium and phosphate hemostasis disorder or systemic mineral imbalance with ectopic calcification of soft tissues
• Current evidence or history of clinically significant corneal or retinal disorder as confirmed by ophthalmologic examination.
• Known untreated central nervous system (CNS) metastases or history of uncontrolled seizures.
• Significant gastrointestinal disorder(s) that could interfere with absorption of futibatinib/binimetinib
• Patients who have neuromuscular disorders that are associated with elevated creatinine kinase (CK)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Futibitanib in combination with binimetinib	Futibatinib and Binimetinib	Dose escalation: Futibitanib in combination with binimetinib in patients with advanced cancer disease. Dose expansion: Futibatinib in combination with binimetinib at the RP2D in patients with advanced KRASmt NSCLC

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) in Part 2	approximately 24 months	proportion of patients who have achieved a PR or complete response (CR) according to RECIST 1.1.
Recommended Phase 2 Dose (RP2D) in Part 1	12 months	Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities

Secondary Outcome Measures

Name	Time	Method
PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032	approximately 24 months	Plasma concentrations of futibatinib, binimetinib, and AR00426032
Duration of response (DOR)	approximately 24 months	DOR is defined as the length of time between first response and the date of objectively documented progression of disease or death
Disease control rate (DCR) at 24 months	approximately 24 months	DCR is defined as the percentage of patients who have achieved a CR, PR, or SD.
PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032	approximately 24 months	Plasma concentrations of futibatinib, binimetinib, and AR00426032
Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032	approximately 24 months	Plasma concentrations of futibatinib, binimetinib, and AR00426032
PK: Accumulation ratio of Cmax and AUC (R) of futibatinib, binimetinib, and AR00426032	approximately 24 months	Plasma concentrations of futibatinib, binimetinib, and AR00426032
Progression-free survival (PFS)	approximately 24 months	PFS is defined as the time from date of first dose to objectively documented progression of disease or death
Number of patients with treatment-emergent adverse events as assessed by CTCAE v5.0	Approximately 24 months	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
PK: Terminal elimination half-life (T1/2) of futibatinib, binimetinib, and AR00426032	approximately 24 months	Plasma concentrations of futibatinib, binimetinib, and AR00426032
PK: Minimum plasma concentration before administration (Cmin) of futibatinib, binimetinib, and AR00426032	approximately 24 months	Plasma concentrations of futibatinib, binimetinib, and AR00426032

Trial Locations

Locations (3)

Community Cancer Center North; 🇺🇸 Indianapolis, Indiana, United States

University of California Los Angeles UCLA Cancer; 🇺🇸 Santa Monica, California, United States

The University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States