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

Sponsor

Taiho Oncology, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04601857

Collaborator

Merck Sharp & Dohme LLC (Industry)

Enrollment

Locations

Arms

41.3

Anticipated Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Advanced and Metastatic Urothelial Cancer	Drug: futibatinib and pembrolizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

46 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jan 21, 2021

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: futibatinib and pembrolizumab (Cohort A) Patients with UC and FGFR3 mutation or FGFR1-4 fusion/rearrangement.	Drug: futibatinib and pembrolizumab Patients will receive futibatinib at an oral dose of 20 mg daily and pembrolizumab at an intravenous dose of 200 mg every 3 weeks Other Names: TAS120 and MK3475
Experimental: futibatinib and pembrolizumab (Cohort B) 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 Patients will receive futibatinib at an oral dose of 20 mg daily and pembrolizumab at an intravenous dose of 200 mg every 3 weeks Other Names: TAS120 and MK3475

Arm

Intervention/Treatment

Experimental: futibatinib and pembrolizumab (Cohort A)

Patients with UC and FGFR3 mutation or FGFR1-4 fusion/rearrangement.

Drug: futibatinib and pembrolizumab

Patients will receive futibatinib at an oral dose of 20 mg daily and pembrolizumab at an intravenous dose of 200 mg every 3 weeks

Other Names:

TAS120 and MK3475

Experimental: futibatinib and pembrolizumab (Cohort B)

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

Patients will receive futibatinib at an oral dose of 20 mg daily and pembrolizumab at an intravenous dose of 200 mg every 3 weeks

Other Names:

TAS120 and MK3475

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [Approximately 12 months]
Objective response rate (ORR), defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR).

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCSF Helen Diller Family Comprehensive Cancer Center	San Francisco	California	United States	94158
2	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02215
3	Henry Ford Hospital	Detroit	Michigan	United States	48202
4	Comprehensive Care Centers of Nevada	Las Vegas	Nevada	United States	89148
5	Centre Georges-François Leclerc	Dijon		France	21079
6	Centre Leon Berard - departement d'oncologie medicale	Lyon		France	69373
7	Institut Paoli Calmettes - HÃ´pital de jour	Marseille		France	13273
8	ICANS - Institut de cancérologie de Strasbourg Europe	Strasbourg		France	67200
9	Centre Regional de Lutte Contre le Cancer de Lorraine	Vandœuvre-lès-Nancy		France	54500
10	Institut De Cancerologie Gustave Roussy	Villejuif		France	94805
11	Hospital Clinic de Barcelona	Barcelona		Spain	08036
12	Hospital de La Santa Creu i Sant Pau	Barcelona		Spain	8025
13	Hospital Universitario Vall d'Hebrón	Barcelona		Spain	8035
14	Hospital Universitario Reina Sofia	Córdoba		Spain	14004
15	Hospital Universitario HMN Sanchinarro	Madrid		Spain	28050
16	ALTHAIA, Xarxa Assistencial Universitària de Manresa	Manresa		Spain	8243
17	Hospital Universitario Marqués de Valdecilla	Santander		Spain	39008
18	Hospital la Fe	Valencia		Spain	46026