A Phase 2 Study Evaluating Futibatinib (TAS-120) Plus Pembrolizumab in the Treatment of Advanced or Metastatic bladder, urethra or pelvis cancer

Phase 1

Conditions: Advanced or Metastatic Urothelial Carcinoma
MedDRA version: 20.0Level: LLTClassification code: 10064467Term: Urothelial carcinoma Class: 10029104
MedDRA version: 20.0Level: LLTClassification code: 10077056Term: Urothelial carcinoma recurrent Class: 10029104
Therapeutic area: Diseases [C] - Neoplasms [C04]

Registration Number: CTIS2024-513760-26-00

Lead Sponsor: Taiho Oncology Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 16

Inclusion Criteria

1. Histologically confirmed advanced or metastatic UC in patients 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. a. In safety lead-in: enrollment regardless of FGFR status b. Cohort A: must have an FGFR3 mutation or FGFR1-4 fusion/rearrangement c. Cohort B: all other patients with UC (including patients with other FGFR or nonFGFR genetic aberrations and patients with WT [nonmutated] tumors), 10. A male patient must agree to use contraception during the treatment period and for at least 6 months following the last dose of study treatment., 11. A female patient is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: a. Not a woman of childbearing potential (WOCBP). b. A WOCBP who agrees to follow contraceptive guidance during the treatment period and for at least 6 months after the last dose of study treatment. c. A WOCBP who has a negative serum pregnancy test within 7 days prior to treatment., 12. Ability to take medications orally (feeding tube is not permitted)., 13. Willing and able to comply with scheduled visits and study procedures., 2. Unfit for or intolerant to cisplatin 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 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. Please refer to protocol for addition inclusion criteria., 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: a. Absolute neutrophil count (ANC) =1.5 × 109 /L b. Platelet count =100,000/mm3 c. Hemoglobin =9.0 g/dL d. Alanine aminotransferase (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. e. Total bilirubin =1.5 × ULN, or =3.0 × ULN for patients with Gilbert's syndrome. f. Creatinine clearance (Ccr) (calculated or measured value): =30 mL/min. For calculated Ccr, use the Cockcroft-Gault formula. g. International normalized ratio (INR) OR prothrombin time =1.5 × ULN unless participant is receiving anticoagulant therapy as long as prothrombin time or aPTT is within therapeutic range of intended use of anticoagulants h. Phosphorus <1.5 ULN, 7. Adequate recovery from the side effects of any prior therapy for nonmetastatic disease (generally defined as recovery of all AEs due to = Grade 1 or baseline; however, patients with = Grade 2 neuropathy, anemia, alopecia, and skin pigmentation may be eligible)., 8. Have provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffi

Exclusion Criteria

1. Have received prior therapy with anti-PD-1, anti-PD-L1/L2 agent., 3. History and/or current evidence of any of the following disorders: a. Non-tumor related alteration of the calcium-phosphorus homeostasis that is considered clinically significant in the opinion of the Investigator b. 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 c. Retinal or corneal disorder confirmed by retinal/corneal examination and considered clinically significant in the opinion of the Investigator., 4. Corrected QT interval using Fridericia's formula (QTcF) >470 msec. Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply., 5. Has received major surgery within the previous 4 weeks., 6. Has received any non-investigational anticancer therapy within the previous 3 weeks (mitomycin within the previous 5 weeks)., 7. 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., 8. 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., 9. A serious illness or medical condition(s) including, but not limited to, the following: a. Has an active infection requiring systemic therapy. b. Myocardial infarction, severe/unstable angina, or symptomatic congestive heart failure within the previous 6 months c. History or current evidence of uncontrolled ventricular arrhythmia d. Chronic diarrhea diseases considered to be clinically significant in the opinion of the Investigator e. Congenital long QT syndrome, or any known history of torsade de pointes, or family history of unexplained sudden death f. 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. g. Have a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis. h. Have had an allogenic tissue/ organ transplant., Please refer to protocol for addition exclusion criteria., 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 HCV RNA results greater than the lower limits of detection of the assay., 11. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the objective response rate (ORR) of futibatinib in<br>combination with pembrolizumab in patients with advanced or<br>metastatic UC who are not candidates to receive a platinum-based<br>treatment regimen.;Secondary Objective: •To assess the safety of futibatinib in combination with pembrolizumab., •To evaluate the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS).;Primary end point(s): Objective response rate (ORR), defined as the proportion of patients experiencing a best overall response of complete response (CR) or partial response (PR).

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):-Disease control rate (DCR), defined as the proportion of patients experiencing a best overall response of stable disease (SD), PR, or CR.;Secondary end point(s):·Duration of response (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.;Secondary end point(s):·Progression-free survival (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.;Secondary end point(s):·Overall survival (OS), defined as the time from the date of the first dose to the death date.;Secondary end point(s):·Safety and tolerability, based on reported adverse events (AEs) and on-study laboratory parameters, graded according to the National Cancer Institute – Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0.