Clinical trial NCT04601857: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Advanced and Metastatic Urothelial Cancer
Keywords: Futibatinib
Pembrolizumab
Urothelial cancer
FGFR
TAS120
MK3475 B04
Lead sponsor: Taiho Oncology, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-10-26
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: Approximately 12 months
Secondary outcomes:
measure: Disease control rate (DCR)
timeFrame: Approximately 8 months
measure: Duration of response (DOR)
timeFrame: Approximately 8 months
measure: Progression-free survival (PFS)
timeFrame: Approximately 8 months
measure: Overall survival (OS)
timeFrame: Approximately 18 months
measure: Incidence of treatment-emergent Adverse Events (AE)[Safety and Tolerability]
timeFrame: Approximately 8 months
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Helen Diller Family Comprehensive Cancer Center
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Care Centers of Nevada
state: Nevada
city: Strasbourg
country: France
facility: ICANS - Institut de cancérologie de Strasbourg Europe
state: Bas-Rhin
city: Marseille
country: France
facility: Institut Paoli Calmettes - HÃ´pital de jour
state: Bouches-du-Rhône
city: Dijon
country: France
facility: Centre Georges-François Leclerc
state: Côte d'Or
city: Lyon
country: France
facility: Centre Leon Berard - departement d'oncologie medicale
state: Rhone
city: Vandœuvre-lès-Nancy
country: France
facility: Centre Regional de Lutte Contre le Cancer de Lorraine
city: Villejuif
country: France
facility: Institut De Cancerologie Gustave Roussy
city: Manresa
country: Spain
facility: ALTHAIA, Xarxa Assistencial Universitària de Manresa
state: Brcelona
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Barcelona
country: Spain
facility: Hospital de La Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital Universitario Vall d'Hebrón
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Madrid
country: Spain
facility: Hospital Universitario HMN Sanchinarro
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Valencia
country: Spain
facility: Hospital la Fe
Study officials:
References: