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

A Phase 1b/2 Open-label, Nonrandomized Study of FGFR Inhibitor Futibatinib in Combination With MEK-inhibitor Binimetinib in Patients With Advanced KRAS Mutant Cancer

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

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Taiho Oncology, INC; Phone Number: 609-250-7336; Email: clinicaltrialinfo@taihooncology.com

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • University of California Los Angeles UCLA Cancer
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Community Cancer Center North
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Futibitanib in combination with 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	Drug: Futibatinib and Binimetinib; Patients will receive futibatinib once daily in combination with binimetinib twice daily by oral administration on a 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (RP2D) in Part 1	Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities	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.	approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
PK: Terminal elimination half-life (T1/2) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
PK: Minimum plasma concentration before administration (Cmin) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
PK: Accumulation ratio of Cmax and AUC (R) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	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	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	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.	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	Approximately 24 months

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2021
• Primary Completion (Actual): June 11, 2023
• Study Completion (Actual): September 21, 2023

Study Registration Dates

• First Submitted: July 6, 2021
• First Submitted That Met QC Criteria: July 14, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: NSCLC; FGFR; Binimetinib; MEKi; Futibatinib; TAS-120; FGFRi; KRASmt
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Antineoplastic Agents; Futibatinib
• Other Study ID Numbers: TAS-120-204

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No