Clinical Trials /

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

NCT04601857

Description:

The purpose of the trial is to evaluate a response to combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or spreading urothelial cancer who are not candidates to receive a platinum-based treatment regimens. It also will help us to learn about the side effects of this combination therapy. This study will also help us to find the futibatinib and pembrolizumab predictive markers of response (i.e. benefit from specific treatment; helps to select particular treatment over another). Another objective is to evaluate the supposed futibatinib and pembrolizumab combination's immunomodulatory effects (i.e. Drug that modifies the immune response or the functioning of the immune system as by the stimulation of antibody formation or the inhibition of white blood cell activity). By conducting this study, we will learn about the variability in drug concentrations within a patient population receiving clinically relevant doses of a futibatinib and pembrolizumab. Pharmacokinetics allows us to examine how the body processes a drug.

Related Conditions:
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: TAS-120-203
  • NCT ID: NCT04601857

Conditions

  • Advanced and Metastatic Urothelial Cancer

Interventions

DrugSynonymsArms
Futibatinib and PembrolizumabTAS120 and MK3475Futibatinib and Pembrolizumab (Cohort A)

Purpose

The purpose of the trial is to evaluate a response to combination of Fibroblast Growth Factor Receptor (FGFR) inhibitor futibatinib and anti-programmed cell death-1 (PD-1) antibody pembrolizumab in patients with advanced or spreading urothelial cancer who are not candidates to receive a platinum-based treatment regimens. It also will help us to learn about the side effects of this combination therapy. This study will also help us to find the futibatinib and pembrolizumab predictive markers of response (i.e. benefit from specific treatment; helps to select particular treatment over another). Another objective is to evaluate the supposed futibatinib and pembrolizumab combination's immunomodulatory effects (i.e. Drug that modifies the immune response or the functioning of the immune system as by the stimulation of antibody formation or the inhibition of white blood cell activity). By conducting this study, we will learn about the variability in drug concentrations within a patient population receiving clinically relevant doses of a futibatinib and pembrolizumab. Pharmacokinetics allows us to examine how the body processes a drug.

Detailed Description

      This study is an open-label, nonrandomized, multicenter Phase 2 study evaluating the
      combination of futibatinib and pembrolizumab in patients with advanced or metastatic UC who
      are not candidates to receive a platinum-based treatment regimen.

      Approximately 46 subjects advanced or metastatic Urothelial Cancer (UC) will be enrolled in
      the trial at approximately 15-17 sites worldwide:

        -  6 patients in the safety lead-in

        -  20 patients with tumors characterized by specific genetic abnormalities (Cohort A)

        -  20 patients with tumors not characterized by specific genetic abnormalities (Cohort B).

      A treatment cycle is defined as 21 days. All enrolled participants will receive the same
      treatment

        -  Futibatinib at an oral (PO) dose of 20 mg daily (5 tablets) (QD); and

        -  Pembrolizumab at an intravenous (I.V.) dose of 200 mg every 3 weeks (Q3W).

      Treatment will continue until disease progression, unacceptable side effects, or any other of
      the criteria for treatment discontinuation is met; of note, pembrolizumab may be administered
      for a maximum of 35 doses or a maximum duration of 2 years, whichever is earlier. The study
      will begin with a safety lead-in period. During this period, a total of 6 patients with
      advanced or metastatic urothelial carcinoma will be enrolled and treated for at least one
      21-day cycle. Patients will be enrolled into this initial safety lead-in period without
      regard for FGFR alteration status.
    

Trial Arms

NameTypeDescriptionInterventions
Futibatinib and Pembrolizumab (Cohort A)ExperimentalPatients with UC and FGFR3 mutation or FGFR1-4 fusion/rearrangement.
  • Futibatinib and Pembrolizumab
Futibatinib and Pembrolizumab (Cohort B)ExperimentalAll 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).
  • Futibatinib and Pembrolizumab

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically confirmed advanced or metastatic urothelial carcinoma who have not
             received systemic treatment for advanced metastatic disease. For patients who received
             prior adjuvant/neoadjuvant chemotherapy or chemo-radiation for urothelial carcinoma, a
             treatment-free interval >12 months between the last treatment administration and the
             date of recurrence is required in order to be considered treatment-naïve in the
             metastatic setting.

               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)

          2. Unfit for or intolerant to standard platinum-based chemotherapy as defined by any one
             of the following criteria:

             a. Chronic kidney disease characterized by the estimated creatinine clearance rate
             (eCCr) per Cockcroft-Gault formula of <60 mL/min or estimated glomerular filtration
             rate (eGFR) of <60 mL/min/1.73 m2, corresponding to NCI-CTCAE v.5.0 Grade ≥2

             b. Impaired hearing (measured by audiometry) of >25 decibel (dB) at two contiguous
             test frequencies in at least one ear, corresponding to NCI-CTCAE v.5.0 Grade ≥2

             c. Peripheral sensory neuropathy Grade ≥2 by NCI-CTCAE v.5.0

             e. In the opinion of the Investigator, the patient is considered ineligible to receive
             any platinum-based chemotherapy

          3. Be willing and able to provide written informed consent for the trial.

          4. Be ≥ 18 years of age.

          5. Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1.

          6. Adequate organ function as defined by the following criteria:

               1. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L

               2. Platelet count ≥ 100,000/mm3

               3. Hemoglobin ≥ 9.0 g/dL

               4. Alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper
                  limit of normal (ULN); if liver function abnormalities are due to underlying
                  liver metastasis, AST and ALT ≤ 5.0 × ULN.

               5. Total bilirubin ≤ 1.5 × ULN, or ≤ 3.0 × ULN for patients with Gilbert's syndrome.

               6. Creatinine clearance (Ccr) (calculated or measured value): ≥30 mL/min. For
                  calculated Ccr, use the Cockcroft-Gault formula.

               7. International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 × ULN unless
                  participant is receiving anticoagulant therapy as long as PT or Activated partial
                  thromboplastin time (aPTT) is within therapeutic range of intended use of
                  anticoagulants

               8. Phosphorus <1.5 ULN

          7. Have a measurable disease per RECIST 1.1, as assessed by the local site
             Investigator/radiology. Lesions situated in a previously irradiated area are
             considered measurable if progression has been demonstrated in such lesions.

        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, including but not limited to soft tissue,
                  kidneys, intestine, or myocardia and lung, considered clinically significant in
                  the opinion of the Investigator

               3. Retinal or corneal disorder confirmed by retinal/corneal examination and
                  considered clinically significant in the opinion of the Investigator.

          3. Has received major surgery within the previous 4 weeks.

          4. Has received any non-investigational anticancer therapy within the previous 3 weeks
             (mitomycin within the previous 5 weeks).

          5. Is currently participating in a study of an investigational agent/device, or has
             participated in a study of an investigational agent or used an investigational device
             within 4 weeks prior to the first dose of study treatment.

          6. Has received a live vaccine within 30 days prior to the first dose of study drug.
             Examples of live vaccines include, but are not limited to, the following: measles,
             mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus
             Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection
             are generally killed virus vaccines and are allowed; however, intranasal influenza
             vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.

          7. Have an active autoimmune disease that has required systemic treatment in the past 2
             years (that is, with use of disease modifying agents, corticosteroids, or
             immunosuppressive drugs). Replacement therapy (for example, thyroxine, insulin, or
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)
             is not considered a form of systemic treatment and is allowed.

          8. Have a history of (noninfectious) pneumonitis that required steroids or has current
             pneumonitis.

          9. Have had an allogenic tissue/ organ transplant.

         10. 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. Active Hepatitis C is defined by a known
             positive Hep C Ab result and known quantitative Hepatitis C virus (HCV) RNA results
             greater than the lower limits of detection of the assay.

         11. Have known active central nervous system metastases and/or carcinomatous meningitis.

         12. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

         13. Has a known additional malignancy that is progressing or has required active treatment
             within the past 2 years

         14. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description:Objective response rate (ORR), defined as the proportion of patients experiencing a best overall response of partial response (PR) or complete response (CR).

Secondary Outcome Measures

Measure:Disease control rate (DCR) in both Cohorts A and B
Time Frame:Approximately 8 months
Safety Issue:
Description:DCR defined as the proportion of patients experiencing a best overall response of stable disease (SD), PR, or CR.
Measure:Duration of response (DOR)in both Cohorts A and B
Time Frame:Approximately 8 months
Safety Issue:
Description: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.
Measure:Progression-free survival (PFS) in both Cohorts A and B
Time Frame:Approximately 8 months
Safety Issue:
Description: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.
Measure:Overall survival (OS) in both Cohorts A and B
Time Frame:Approximately 18 months
Safety Issue:
Description:OS defined as the time from the date of the first dose to the death date.
Measure:Incidence of treatment-emergent Adverse Events (AE)[Safety and Tolerability]in both Cohorts A and B
Time Frame:Approximately 8 months
Safety Issue:
Description:Safety and tolerability of the futibatinib and pembolizumab combination therapy based on reported AEs, graded according to the NCI-CTCAE, Version 5.0

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Taiho Oncology, Inc.

Trial Keywords

  • Futibatinib
  • Pembrolizumab
  • Urothelial cancer
  • FGFR
  • TAS120
  • MK3475 B04

Last Updated

October 26, 2020