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

Taiho Pharma

Status and phase: Terminated; Phase 2

Conditions: Advanced and Metastatic Urothelial Cancer

Treatments: Drug: Pembrolizumab; Drug: Futibatinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT04601857

2020-000945-15 (EudraCT Number)

TAS-120-203

Details and patient eligibility

About

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.

Enrollment: 43 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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43 participants in 2 patient groups

Cohort A

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Futibatinib

Cohort B

Experimental group

Description:

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.

Treatment:

Drug: Pembrolizumab

Drug: Futibatinib