Clinical trial NCT04965818: Phase 1b/2 Study of Futibatinib in Combination With Binimetinib in Patients With Advanced KRAS Mutant Cancer
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations
Non-Small Cell Lung Cancer
KRAS Gene Mutation
Keywords: Futibatinib
Binimetinib
MEKi
FGFR
FGFRi
TAS-120
KRASmt
NSCLC
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-16
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Recommended Phase 2 Dose (RP2D) in Part 1
timeFrame: 12 months
measure: Objective Response Rate (ORR) in Part 2
timeFrame: approximately 24 months
Secondary outcomes:
measure: Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032
timeFrame: approximately 24 months
measure: PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032
timeFrame: approximately 24 months
measure: PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032
timeFrame: approximately 24 months
measure: PK: Terminal elimination half-life (T1/2) of futibatinib, binimetinib, and AR00426032
timeFrame: approximately 24 months
measure: PK: Minimum plasma concentration before administration (Cmin) of futibatinib, binimetinib, and AR00426032
timeFrame: approximately 24 months
measure: PK: Accumulation ratio of Cmax and AUC (R) of futibatinib, binimetinib, and AR00426032
timeFrame: approximately 24 months
measure: Duration of response (DOR)
timeFrame: approximately 24 months
measure: Progression-free survival (PFS)
timeFrame: approximately 24 months
measure: Disease control rate (DCR) at 24 months
timeFrame: approximately 24 months
measure: Number of patients with treatment-emergent adverse events as assessed by CTCAE v5.0
timeFrame: Approximately 24 months
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: University of California Los Angeles UCLA Cancer
state: California
city: Indianapolis
country: United States
facility: Community Cancer Center North
state: Indiana
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
Study officials:
References: