Advanced or Metastatic Solid Tumors Irrespective of Gene Alterations, KRAS Gene Mutation, Non-Small Cell Lung Cancer
Conditions
Keywords
Futibatinib, Binimetinib, MEKi, FGFR, FGFRi, TAS-120, KRASmt, NSCLC
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.
Interventions
DRUGFutibatinib and Binimetinib
Patients will receive futibatinib once daily in combination with binimetinib twice daily by oral administration on a 21-day cycle
Sponsors
Taiho Oncology, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (RP2D) in Part 1 | 12 months | Determine RP2D of futibatinib in combination with binimetinib based on Dose Limiting Toxicities |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK): Maximum plasma concentration (Cmax) of futibatinib, binimetinib, and AR00426032 | approximately 24 months | Plasma concentrations of futibatinib, binimetinib, and AR00426032 |
| PK: Area under the plasma concentration-time curve (AUC) of futibatinib, binimetinib, and AR00426032 | approximately 24 months | Plasma concentrations of futibatinib, binimetinib, and AR00426032 |
| PK: Time to reach maximum plasma concentration (Tmax) of futibatinib, binimetinib, and AR00426032 | approximately 24 months | Plasma concentrations of futibatinib, binimetinib, and AR00426032 |
| 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 |
| PK: Accumulation ratio of Cmax and AUC (R) 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 |
| 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 |
| 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. |
| 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 |
Countries
United States
Outcome results
None listed