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

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

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.

Study Overview

• Status: Terminated
• Conditions: Advanced and Metastatic Urothelial Cancer
• Intervention / Treatment: Drug: Pembrolizumab; Drug: Futibatinib

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Vandœuvre-lès-Nancy, France, 54500
    • Centre Regional de Lutte Contre le Cancer de Lorraine
  • Villejuif, France, 94805
    • Institut de Cancérologie Gustave Roussy
  • Bas-Rhin
    • Strasbourg, Bas-Rhin, France, 67200
      • ICANS - Institut de Cancerologie de Strasbourg Europe
  • Bouches-du-Rhône
    • Marseille, Bouches-du-Rhône, France, 13273
      • Institut Paoli Calmettes - Hôpital de jour
  • Côte d'Or
    • Dijon, Côte d'Or, France, 21079
      • Centre Georges-François Leclerc
  • Rhone
    • Lyon, Rhone, France, 69373
      • Centre Leon Berard - departement d'oncologie medicale
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona
  • Barcelona, Spain, 8025
    • Hospital de La Santa Creu i Sant Pau
  • Barcelona, Spain, 8035
    • Hospital Universitario Vall d'Hebron
  • Córdoba, Spain, 14004
    • Hospital Universitario Reina Sofia
  • Madrid, Spain, 28050
    • Hospital Universitario HMN Sanchinarro
  • Santander, Spain, 39008
    • Hospital Universitario Marqués de Valdecilla
  • Valencia, Spain, 46026
    • Hospital La Fe
  • Brcelona
    • Manresa, Brcelona, Spain, 8243
      • Althaia, Xarxa Assistencial Universitària de Manresa
• United States
  • California
    • San Francisco, California, United States, 94158
      • UCSF Helen Diller Family Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Care Centers of Nevada

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent for the trial.
2. Age ≥ 18 years of age

3. Histologically confirmed advanced or metastatic urothelial carcinoma who have not received systemic treatment for advanced metastatic disease.

   1. Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement.
   2. 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)
4. Unfit for or intolerant to standard platinum-based chemotherapy.
5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.
6. Adequate organ function.
7. Have a measurable disease per RECIST 1.1

Exclusion Criteria:

1. Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent or FGFR inhibitor.

2. History and/or current evidence of any of the following disorders:

   1. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator.
   2. Ectopic mineralization/calcification considered clinically significant in the opinion of the Investigator.
   3. Retinal or corneal disorder considered clinically significant in the opinion of the Investigator.
3. Has received a live vaccine within 30 days prior to the first dose of study drug.
4. Have an active autoimmune disease that has required systemic treatment in the past 2 years.
5. Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis.
6. Have had an allogenic tissue/ organ transplant.
7. 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.
8. Have known active central nervous system metastases and/or carcinomatous meningitis.
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
10. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort A; Participants with metastatic urothelial carcinoma (UC) and FGFR3 mutation or FGFR1-4 fusion/rearrangement received futibatinib 20 milligrams (mg), orally, once daily (QD), in a 21-day cycle for maximum duration of 590 days along with pembrolizumab 200 mg, intravenously (IV), every 3 weeks (Q3W), in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years.	Drug: Pembrolizumab; IV; Other Names: KEYTRUDA; MK-3475-B04; Drug: Futibatinib; Oral; Other Names: TAS120
Experimental: Cohort B; Participants with metastatic UC (including participants with other FGFR or non-FGFR genetic aberrations and participants with wild type [non-mutated] tumors) received futibatinib 20 mg, orally, QD, in a 21-day cycle for maximum duration of 563 days along with pembrolizumab 200 mg, IV, Q3W in a 21-day cycle for a maximum of 35 doses or a maximum duration of 2 years.	Drug: Pembrolizumab; IV; Other Names: KEYTRUDA; MK-3475-B04; Drug: Futibatinib; Oral; Other Names: TAS120

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the proportion of participants experiencing a best overall response of partial response (PR) or complete response (CR) according to response evaluation criteria in solid tumors, version 1.1 (RECIST 1.1) criteria based on investigator assessment. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30 percent (%) decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to less than (<)10 millimeters (mm).	Up to 38 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Control Rate (DCR)	DCR was defined as the proportion of participants experiencing a best overall response of SD, PR, or CR. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), referencing the smallest sum diameters while on study. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis <10 mm.	Up to 38 months
Duration of Response (DOR)	DOR was calculated for all responders from the date of first documentation of response (CR or PR) to the first documentation of objective tumor progression or death due to any cause, whichever occurred first. Evaluation of target lesions defined a CR as the disappearance of all target lesions and non-target lesions (if applicable), and normalization of tumor marker level; PR was defined as at least a 30% decrease in the sum of diameters of the target lesions, taking as a reference the baseline sum of diameters for all target lesion assessments. Evaluation of non-target lesions was defined as the persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. For both target and non-target evaluations, any pathological lymph node must have had a reduction in short axis to <10 mm.	Up to 38 months
Progression-free Survival (PFS)	PFS was defined as the time from the first dose of study therapy to the date of death (any cause) or disease progression, whichever occurred first. The PFS was analyzed using a Kaplan-Meier method, with PFS time being censored on the date of the last tumor assessment. The 95% confidence interval (CI) for median PFS was provided using the Kaplan-Meier procedure.	Up to 38 months
Overall Survival (OS)	OS was defined as the time from the date of the first dose to the death date. Participants without a documented death date were censored on the last date they were known to be alive.	Up to 38 months
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant and does not necessarily have a causal relationship with the study drug. TEAEs are defined as AEs reported up to 30 days after the last dose of any study therapy (safety follow-up) or until the start of new antitumor therapy, whichever is earlier, unless otherwise specified.	Up to 38 months

Collaborators and Investigators

• Sponsor: Taiho Oncology, Inc.
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 7, 2021
• Primary Completion (Actual): March 8, 2024
• Study Completion (Actual): September 16, 2025

Study Registration Dates

• First Submitted: October 15, 2020
• First Submitted That Met QC Criteria: October 22, 2020
• First Posted (Actual): October 26, 2020

Study Record Updates

• Last Update Posted (Actual): December 31, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Pembrolizumab; FGFR; Urothelial cancer; Futibatinib; TAS120; MK3475 B04
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Transitional Cell; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab; futibatinib
• Other Study ID Numbers: TAS-120-203; 2020-000945-15 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No