Futibatinib in Combination With Durvalumab Prior to Cystectomy for the Treatment of Muscle-Invasive Bladder Cancer Patients Who Are Ineligible for Cisplatin-based Therapy

Recruiting now · Phase 2

Conditions studied: Bladder Urothelial Carcinoma, Muscle Invasive Bladder Carcinoma, Stage II Bladder Cancer AJCC v8, Stage IIIA Bladder Cancer AJCC v8

In brief

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.

Key facts

Study ID

NCT06263153

Run by

Yuanquan Yang

People needed

24

Starts

2024-12-30

Expected to finish

2026-12-31

Last updated by the study team

2025-12-17

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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)

You may not qualify if…

• Women who are pregnant or breastfeeding
• Male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy
• Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks before the first dose of trial treatment
• Has upper tract urothelial carcinoma
• Has small-cell carcinoma component on histology
• Evidence of measurable nodal or metastatic disease
• Concurrent anticancer therapy (e.g., chemotherapy, radiation therapy, surgery, immunotherapy, biologic therapy, hormonal therapy, investigational therapy, intravesical therapy, or tumor embolization)
• Received prior systemic chemotherapy for muscle-invasive bladder cancer at any time in the patient's medical history
• Has received anti-PD-1/PD-L1 therapy or FGFR inhibitor previously for MIBC, except if used in earlier stage urothelial carcinoma such as non-muscle invasive bladder cancer (NMIBC) and completed > 3 months prior to registration
• Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
• All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline prior to screening for this study.
• Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
• Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE, not have experienced recurrence of an AE if re-challenged, and not currently require maintenance doses of > 10 mg prednisone or equivalent per day.
• Underwent major surgery and has not recovered adequately from the intervention's toxicity and/or complications before starting therapy
• Has an active second malignancy except for low-risk localized prostate cancer on "watch and wait"
• Subjects with a history of malignancy that has been completely treated, with no evidence of active cancer for 2 years before enrollment, or subjects with surgically cured tumors with a low risk of recurrence are allowed to enroll at PI's discretion (e.g. adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease and effectively treated carcinoma in situ without evidence of disease).
• Has active cardiac disease, defined as:
• Myocardial infarction or unstable angina pectoris within 3 months of the first date of study therapy
• Unstable arrhythmias
• Decompensated heart failure
• Uncontrolled hypertension and unstable angina pectoris
• Average QT corrected by the Fridericia formula (QTcF) > 470 msec (males and females) (Note: If the QTcF is > 470 msec in the first electrocardiography [ECG], a total of 3 ECGs separated by >= 5 minutes should be performed. If the average of these 3 consecutive results for QTcF is =< 470 msec, the subject meets eligibility in this regard.)
• Has any medical condition that may prevent the patient from undergoing radical cystectomy
• Must be at least 2 weeks beyond high-dose systemic corticosteroids; chronic steroid use up to 10 mg daily prednisone (or equivalent), intranasal, inhaled, topical steroids, local steroid injections (e.g., intra articular injection), steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication) are permitted
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [e.g., colitis or Crohn's disease], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:

Where it is running

• Cleveland Clinic Taussig Cancer Center — Cleveland, Ohio, United States (enrolling)
• Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (enrolling)
• University of Michigan Comprehensive Cancer Center — Ann Arbor, Michigan, United States

Full record on ClinicalTrials.gov

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