An Open Label, Single-arm, Phase 2 Study of Neoadjuvant Nivolumab and Nab-paclitaxel Before Radical Cystectomy for Patients With Muscle-invasive Bladder Cancer (NURE-Combo)

To assess whether nivolumab+nab-paclitaxel combination results in patients with muscle-invasive bladder cancer

This is a Phase 2, single-center, open-label, non-randomized study in patients with muscle-invasive urothelial carcinoma of the bladder. The general framework of the study will be as follows: A transurethral resection of the bladder for biopsy, histological characterization, and local staging will be executed first. With the aim to improve the sensitivity of CT scan in assessing pelvic lymph-nodes and better assess the local extent of bladder tumor, computed tomography (CT) scan, 18FDG-PET/CT scan, and multiparametric bladder MRI (mpMRI) will be done during screening and before cystectomy to stage and evaluate response. Eligible patients will receive neoadjuvant treatment: 360 mg nivolumab IV on Day 1 plus 125 mg/m2 nab-paclitaxel on Day 1 and 8, in a 21-day cycle. A total of 4 cycles are planned before surgery. Surgery will be planned at the time of study inclusion to be done within 3 weeks of the last dose of study drug. Dose reductions will be applied depending on the severity of AEs, and treatment interruption or discontinuation criteria will be fully described in the protocol. After surgery, patients will receive 12-month adjuvant therapy with nivolumab 360 mg IV, every 3 weeks. RECIST v1.1 criteria will be used to assess patient response to treatment by determining tumor size and PFS. Screening assessments should be performed no more than 21 days prior to the start of study treatment. Following the screening assessment, subsequent assessments will be carried out after the administration of the study drugs prior to cystectomy. If an unscheduled assessment is performed and the patient has not progressed, the results should be reported at the next scheduled visit. The method of tumor assessment used at baseline e.g. CT or MRI scans chest, abdomen, pelvis, must be used at each sub-sequent follow-up assessment. Patients will be monitored carefully for the development of adverse events and will be monitored for clinical and/or radiographic evidence of disease progression according to usual standards of clinical practice. Adverse experiences will be evaluated according to criteria outlined in the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5.0.