Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma

Study Overview
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Brief Summary
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The purpose of the trial is to evaluate the antitumor activity and confirm the safety for the combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or metastatic urothelial cancer who are not candidates to receive a platinum-based treatment regimens.

Official Title
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A Phase 2 Study Evaluating Futibatinib (TAS 120) Plus Pembrolizumab in the Treatment of Advanced or Metastatic Urothelial Carcinoma

Conditions
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Advanced and Metastatic Urothelial Cancer

Intervention / Treatment
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* Drug: futibatinib and pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent for the trial. Age ≥ 18 years of age Histologically confirmed advanced or metastatic urothelial carcinoma who have not received systemic treatment for advanced metastatic disease. Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement. Cohort B: all other patients with UC (including patients with other FGFR or non-FGFR genetic aberrations and patients with wild-type [non-mutated] tumors) Unfit for or intolerant to standard platinum-based chemotherapy. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1. Adequate organ function. Have a measurable disease per RECIST 1.1 Exclusion Criteria: Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent or FGFR inhibitor. History and/or current evidence of any of the following disorders: Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator. Ectopic mineralization/calcification considered clinically significant in the opinion of the Investigator. Retinal or corneal disorder considered clinically significant in the opinion of the Investigator. Has received a live vaccine within 30 days prior to the first dose of study drug. Have an active autoimmune disease that has required systemic treatment in the past 2 years. Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. Have had an allogenic tissue/ organ transplant. Has known human immunodeficiency virus (HIV) and/or history of Hepatitis B or C infections, or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. Have known active central nervous system metastases and/or carcinomatous meningitis. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: futibatinib and pembrolizumab (Cohort A)<br>Patients with UC and FGFR3 mutation or FGFR1-4 fusion/rearrangement. | Drug: futibatinib and pembrolizumab<br>* Patients will receive futibatinib at an oral dose of 20 mg daily and pembrolizumab at an intravenous dose of 200 mg every 3 weeks<br>* Other names: TAS120 and MK3475;|
| Experimental: futibatinib and pembrolizumab (Cohort B)<br>All other patients than in Cohort A with UC (including patients with other FGFR or non-FGFR genetic aberrations and patients with wild-type [non-mutated] tumors). | Drug: futibatinib and pembrolizumab<br>* Patients will receive futibatinib at an oral dose of 20 mg daily and pembrolizumab at an intravenous dose of 200 mg every 3 weeks<br>* Other names: TAS120 and MK3475;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Objective response rate (ORR), defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR). | Approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease control rate (DCR) | DCR defined as the proportion of patients experiencing a best overall response of stable disease (SD), PR, or CR. | Approximately 8 months | 
| Duration of response (DOR) | DOR defined as the time from the first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurs first. | Approximately 8 months | 
| Progression-free survival (PFS) | PFS defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression, whichever occurs first. | Approximately 8 months | 
| Overall survival (OS) | OS defined as the time from the date of the first dose to the death date. | Approximately 18 months | 
| Incidence of treatment-emergent Adverse Events (AE)[Safety and Tolerability] | Safety and tolerability of the futibatinib and pembolizumab combination therapy based on reported AEs, graded according to the NCI-CTCAE, Version 5.0 | Approximately 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Futibatinib, Pembrolizumab, Urothelial cancer, FGFR, TAS120, MK3475 B04