A Phase II Trial of Futibatinib in Combination With Durvalumab (MEDI4736) Administered to Cisplatin-Ineligible Patients With Muscle-Invasive Bladder Cancer Before Cystectomy
This phase II trial tests how well the combination of futibatinib and durvalumab given before cystectomy works in treating patients with muscle-invasive bladder cancer (MIBC) who are ineligible for cisplatin-based therapy. Cisplatin-based therapy is the standard of care for patients with MIBC. However, many patients cannot receive standard therapy due to poor renal function, peripheral neuropathy, poor functional status, or clinically significant heart failure. Futibatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Durvalumab is a monoclonal antibody that may interfere with the ability of tumor cells to grow and spread. Radical cystectomy is a surgery to remove all of the bladder as well as nearby tissues and organs. Giving futibatinib in combination with durvalumab before surgery may be an effective treatment option for patients with MIBC who are ineligible for cisplatin-based therapy.
• Able to provide signed informed consent
• Female or male subjects \>= 18 years old
• Bodyweight \>30kg
• FGFR1, 2, or 3 overexpression as defined by a score of 3+ or 4+ on ribonucleic acid (RNA) in-situ hybridization (RNAScope assay)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Histologically confirmed urothelial carcinoma of the bladder
‣ Mixed histologies are permitted if urothelial carcinoma is the predominant histology ( \>= 50%)
• Clinical stage T2-T4a, N0, M0 disease by trans urethral removal of bladder tumour (TURBT) and imaging studies (stage II-IIIA per American Joint Committee on Cancer \[AJCC\] 2018)
• Refuse or ineligible for cisplatin-based neoadjuvant chemotherapy as defined by any of the following:
‣ ECOG performance status (PS) \> 1
⁃ Creatinine clearance (calculated or measured) \< 60 mL/min as measured by the Cockcroft-Gault formula
⁃ Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0) grade \>= 2 hearing loss
⁃ CTCAE v 5.0 grade \>= 2 neuropathy
⁃ New York Heart Association (NYHA) class \> II cardiac dysfunction
• Treatment with anti-PD-1/PD-L1 therapy for non-muscle invasive bladder cancer (NMIBC) is permitted if it is completed \> 3 months before registration
• Eligible for radical cystectomy by the following:
‣ Fit and planned for radical cystectomy according to local guidelines
• Archival transurethral resection of bladder tumor (TURBT) tissue submission must be 30 unstained slides. If archival tissue is unavailable, the patient must undergo cystoscopy and biopsy. The tumor sample must contain at least 20% viable tumor
• Evidence of post-menopausal status or negative urinary or serum pregnancy test for female premenopausal patients.
• Female subjects of childbearing potential and male subjects must be willing to completely abstain or agree to use a highly effective method of contraception (i.e., less than 1% failure rate), from the time of signing informed consent and for the duration of study participation through 90 days following the last dose of study drug.
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \> 1500 per mm\^3
• Platelet count \>= 100 x 10\^9/L
• International normalized ratio (INR) or activated partial thromboplastin time (aPTT) \< 1.5 × upper limit of normal (ULN), unless the patient is receiving anticoagulation therapy provided INR or PTT is within the therapeutic range of the intended anticoagulant therapy
• Serum bilirubin =\< 1.5 x institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional upper limit of normal
• Phosphorus ≤ institutional upper limit of normal (ULN)
• Measured creatinine clearance (CL) \> 30 mL/min or calculated creatinine CL \> 30 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• Must have a life expectancy of at least 12 weeks