A Study of TAS-120 in Patients With Advanced Solid Tumors

Study Overview
=================
Brief Summary
-----------------
This is an open-label, nonrandomized, Phase 1/2 study for the fibroblast growth factor receptor (FGFR) inhibitor futibatinib (TAS-120). The purpose of the study is to evaluate the safety, tolerability, PK, pharmacodynamic, and anti-tumor activity of futibatinib in patients with advanced solid tumors with and without genomic FGF/FGFR abnormalities. The study will be conducted in 3 parts: Dose escalation portion to determine the MTD and/ or RP2D of futibatinib. Phase 1 expansion portion to further evaluate the safety and efficacy of futibatinib in patients with tumors harboring FGF/FGFR aberrations, including patients with cholangiocarcinoma (CCA), primary CNS tumors, urothelial carcinoma, breast cancer, gastric cancer. Phase 2 study portion to confirm ORR of futibatinib in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions).

Official Title
-----------------
Phase 1/2 Study of TAS-120 in Patients With Advanced Solid Tumors Harboring FGF/FGFR Aberrations

Conditions
-----------------
Cholangiocarcinoma, Urothelial Cancer, Advanced and Metastatic Cancer Patients With Tumors Harboring FGF/FGFR Tumors, Primary CNS Tumors, Breast Cancer, Gastric Cancer

Intervention / Treatment
-----------------
* Drug: Futibatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provide written informed consent Age ≥ 18 years of age Has histologically or cytologically confirmed, locally advanced or metastatic cancer The following specific criteria for each study portion Phase 1 (Dose Escalation): Patients with any type of solid tumor Disease progression following standard therapies or intolerant to prior standard therapies Phase 1 (Dose Expansion) Have at least one FGF/FGFR aberration Disease progression following standard therapies or were intolerant to prior standard therapies (including prior FGFR inhibitors). Have measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) for advanced solid tumors or RANO criteria (2010) for brain tumors. Patients with any of the following tumor types Patients with intrahepatic or extrahepatic CCA harboring FGFR2 gene fusions or other FGFR2 aberrations Patients with primary CNS tumors Patients with advanced urothelial carcinoma with FGFR3 fusions or FGFR3 activating mutations Patients with breast cancer or gastric cancer Patients with other solid tumor types harboring FGFR gene fusions or activating mutations Patients with solid tumor types and other FGF/FGFR alterations not listed above Phase 2 Patients with iCCA and FGFR2 gene rearrangements (incl fusions) Have been treated with at least one prior systemic gemcitabine and platinum-based chemotherapy Must have documentation of radiographic progression of disease No prior FGFR inhibitor Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) guidelines (version 1.1, 2009) Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 Adequate organ function. Exclusion Criteria: History and/or current evidence of clinically significant non-tumor related alteration of calcium-phosphorus homeostasis. History and/or current evidence of clinically significant ectopic mineralization/calcification. History and/or current evidence of clinically significant retinal disorder A serious illness or medical condition(s) Pregnant or breast-feeding female

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1 Dose escalation<br>Phase 1 Dose escalation portion for once daily and thrice weekly dosing of futibatinib (TAS-120) in patients with solid tumors. | Drug: Futibatinib<br>* oral once daily dosing, 21-day cycle<br>* Other names: TAS-120;|
| Experimental: Phase 1 Dose expansion<br>Phase 1 Dose expansion portion for once daily dosing of futibatinib (TAS-120) in patients with tumors harboring FGF/FGFR aberrations | Drug: Futibatinib<br>* oral once daily dosing, 21-day cycle<br>* Other names: TAS-120;|
| Experimental: Phase 2<br>Phase 2 portion for once daily dosing of futibatinib (TAS-120) in intrahepatic CCA patients with tumors harboring FGFR2 gene rearrangements (incl fusions). | Drug: Futibatinib<br>* oral once daily dosing, 21-day cycle<br>* Other names: TAS-120;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 (Dose escalation): Safety and Recommended Phase 2 Dose (RPTD) |  | Baseline until 30 days after end of study treatment; up to 18 months (estimated) | 
| Phase 1 (Dose expansion): Objective Response Rate (ORR) |  | Baseline to end of study treatment; up to 24 months (estimated) | 
| Phase 2 - Objective Response Rate (ORR) | Objective Response Rate (ORR) by independent review committee according to RECIST guidelines (version 1.1, 2009) | Baseline to end of study treatment; up to 24 months (estimated) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 (Dose escalation): Pharmacokinetics |  | Predose to Day 21 of cycle 1 | 
| Phase 1 (Dose escalation): Pharmacodynamics |  | Predose to Day 21 of cycle 1 | 
| Phase 1 (Dose escalation): - Anti-tumor activity: Objective Response Rate (ORR) |  | Baseline to end of study treatment; up to 24 months (estimated) | 
| Phase 1 (Dose expansion): Safety |  | Baseline until 30 days after end of study treatment; up to 24 months (estimated) | 
| Phase 1 (Dose expansion): Disease Control Rate (DCR) |  | Baseline to end of study treatment; up to 24 months (estimated) | 
| Phase 1 (Dose expansion): Duration of Response (DOR) |  | From onset to end of confirmed response; up to 24 months (estimated) | 
| Phase 1 (Dose expansion): Progression free survival (PFS) |  | Baseline until progressive disease or death; up to 24 months (estimated) | 
| Phase 1 (Dose expansion): Overall survival (OS) |  | Baseline until death; up to 36 months (estimated) | 
| Phase 2: Duration of Response (DOR) |  | From onset to end of confirmed response; up to 24 months (estimated) | 
| Phase 2: Safety |  | Baseline until 30 days after end of study treatment; up to 24 months (estimated) | 
| Phase 2: Disease Control Rate (DCR) |  | Baseline to end of study treatment; up to 24 months (estimated) | 
| Phase 2: Progression free survival (PFS) |  | Baseline until progressive disease or death; up to 24 months (estimated) | 
| Phase 2: Overall survival (OS) |  | Baseline until death; up to 36 months (estimated) | 
| Phase 2: Patient Reported Outcome (PRO) |  | Baseline until 30 days after end of study treatment; up to 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
FGF, FGFR, Futibatinib, TAS-120