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.

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.