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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04965818
• Other study ID #: TAS-120-204
• Status: Terminated
• Phase: Phase 1
• Start date: September 20, 2021
• Est. completion date: September 21, 2023

Study information

• Verified date: October 2023
• Source: Taiho Oncology, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 38
• Est. completion date: September 21, 2023
• Est. primary completion date: June 11, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations
• Carcinoma, Non-Small-Cell Lung
• KRAS Gene Mutation
• Non-Small Cell Lung Cancer

Intervention

Drug:
• Futibatinib and Binimetinib
Patients will receive futibatinib once daily in combination with binimetinib twice daily by oral administration on a 21-day cycle

Locations

Country	Name	City	State
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Community Cancer Center North	Indianapolis	Indiana
United States	University of California Los Angeles UCLA Cancer	Santa Monica	California

Sponsors (1)

Lead Sponsor	Collaborator
Taiho Oncology, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recommended Phase 2 Dose (RP2D) in Part 1	Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities	12 months
Primary	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	Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
Secondary	PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
Secondary	PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
Secondary	PK: Terminal elimination half-life (T1/2) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
Secondary	PK: Minimum plasma concentration before administration (Cmin) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
Secondary	PK: Accumulation ratio of Cmax and AUC (R) of futibatinib, binimetinib, and AR00426032	Plasma concentrations of futibatinib, binimetinib, and AR00426032	approximately 24 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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