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

• ClinicalTrials.gov Identifier: NCT04601857
• Recruitment Status: Active, not recruiting
• First Posted: October 26, 2020
• Last Update Posted: April 12, 2024
• Sponsor: Taiho Oncology, Inc.
• Collaborator: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Taiho Oncology, Inc.

Tracking Information

• First Submitted Date: October 15, 2020
• First Posted Date: October 26, 2020
• Last Update Posted Date: April 12, 2024
• Actual Study Start Date: January 21, 2021
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 20, 2021)

Objective response rate (ORR) [ Time Frame: 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).

Original Primary Outcome Measures (submitted: October 22, 2020)

To evaluate the objective response rate (ORR) of futibatinib in combination with pembrolizumab in patients with advanced or metastatic UC who are not candidates to receive a platinum-based treatment regimen [ Time Frame: 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).

Current Secondary Outcome Measures (submitted: March 15, 2022)

• Disease control rate (DCR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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] [ Time Frame: 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

Original Secondary Outcome Measures (submitted: October 22, 2020)

• Disease control rate (DCR) in both Cohorts A and B [ Time Frame: 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)in both Cohorts A and B [ Time Frame: 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) in both Cohorts A and B [ Time Frame: 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) in both Cohorts A and B [ Time Frame: 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]in both Cohorts A and B [ Time Frame: 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

• Current Other Pre-specified Outcome Measures: Not Provided

Original Other Pre-specified Outcome Measures (submitted: October 22, 2020)

• Explore predictive markers of response to futibatinib and pembrolizumab [ Time Frame: Approximately 18 months ]
  Relationship between FGFR aberrations, PD-L1 status, and status of other biomarkers in the tumor and clinical outcome.
• Evaluate the immunomodulatory effects of the combination of futibatinib and pembrolizumab [ Time Frame: Approximately 12 months ]
  Assess the effect of the combination on T-cells and other biomarkers.
• Estimate maximum plasma concentration [Cmax] of futibatinib at steady-state [ Time Frame: Approximately 12 months ]
  Steady-state Cmax of futibatinib will be estimated using the population pharmacokinetic [PK] analysis. Relationship between Cmax and clinical outcome will be explored.
• Estimate area under the plasma concentration-time curve over the dose interval [AUC] of futibatinib at steady-state [ Time Frame: Approximately 12 months ]
  Steady-state AUC of futibatinib will be estimated using the population PK analysis. Relationship between AUC and clinical outcome will be explored.

Descriptive Information

• Brief Title: Futibatinib and Pembrolizumab Combination in the Treatment of Advanced or Metastatic Urothelial Carcinoma
• Official Title: A Phase 2 Study Evaluating Futibatinib (TAS 120) Plus Pembrolizumab in the Treatment of Advanced or Metastatic Urothelial Carcinoma
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Advanced and Metastatic Urothelial Cancer

Intervention

Drug: futibatinib and pembrolizumab (KEYTRUDA®))

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 Name: TAS120 and MK-3475-B04

Study Arms

• Experimental: futibatinib and pembrolizumab (Cohort A)
  Patients with UC and FGFR3 mutation or FGFR1-4 fusion/rearrangement.
  Intervention: Drug: futibatinib and pembrolizumab (KEYTRUDA®))
• 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).
  Intervention: Drug: futibatinib and pembrolizumab (KEYTRUDA®))

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: October 22, 2020): 46
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: June 30, 2024
• Estimated Primary Completion Date: May 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Spain, United States

Administrative Information

• NCT Number: NCT04601857
• Other Study ID Numbers: TAS-120-203; 2020-000945-15 ( EudraCT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Taiho Oncology, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Taiho Oncology, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Not Provided
• PRS Account: Taiho Oncology, Inc.
• Verification Date: April 2024