Perioperative Durvalumab plus Cisplatin-Based Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Cancer: A Global Open-Label Single-Arm Study

The primary objective is to assess the safety of neoadjuvant durvalumab combined with ddMVAC before radical cystectomy in muscle-invasive bladder cancer, which is clinically relevant for determining perioperative treatment feasibility and risk. The secondary objectives are to further assess the safety and tolerability of perioperative durvalumab with neoadjuvant chemotherapy, and to evaluate efficacy in terms of event-free survival, disease-free survival, overall survival, pathological complete response, and pathological downstaging after radical cystectomy.

The trial population included patients with muscle-invasive bladder cancer, with both female and male participants and an age range corresponding to adults and older adults. A total of 60 participants were enrolled. The population was selected as patients with resectable disease who were planning to undergo radical cystectomy at randomization. Participants were required to have an ECOG performance status of 0 or 1, a life expectancy of at least 12 weeks at first dose, and no prior systemic chemotherapy or immunotherapy for treatment of muscle-invasive bladder cancer. The source did not provide additional lifestyle considerations.

The study is an open-label, single-arm, global trial in adults with muscle-invasive bladder cancer. It evaluates perioperative durvalumab combined with cisplatin-based neoadjuvant chemotherapy before radical cystectomy. The main objective is to assess the safety of neoadjuvant durvalumab with ddMVAC prior to surgery. The overall trial duration is planned from 2026-06-09 to 2028-05-09. Study participation begins with a screening visit to confirm eligibility, including disease stage, surgical plan, performance status, life expectancy, and absence of prior systemic chemotherapy or immunotherapy for this disease. Eligible participants then receive study treatment and undergo follow-up assessments to monitor safety, treatment-emergent adverse events, laboratory findings, and disease outcomes. An end-of-study visit is performed after completion of study procedures or after early discontinuation. The expected period of participant involvement extends from first dose through surgery and subsequent follow-up assessments. Early termination may occur if radical cystectomy is not performed as planned, if disease progression occurs before surgery, if surgery is refused, or if treatment is interrupted or discontinued because of adverse events or other study-related reasons.

Durvalumab was administered as IMFINZI 50 mg/mL concentrate for solution for infusion. The pharmaceutical form was a solution for infusion, and the dose was 1500 mg given by intravenous administration. The study evaluated perioperative durvalumab in combination with ddMVAC prior to radical cystectomy in patients with muscle-invasive bladder cancer. The dosing schedule and administration were conducted according to the study protocol.

Efficacy will be assessed using event-based and pathologic endpoints in participants with muscle-invasive bladder cancer. The efficacy measures of interest include event-free survival, disease-free survival, overall survival, pathologic complete response, and pathologic downstaging. Event-free survival is defined as the time from first neoadjuvant durvalumab plus ddMVAC treatment until the earliest occurrence of disease recurrence after radical cystectomy, documented progression in participants medically precluded from radical cystectomy, or failure to undergo radical cystectomy at the expected time in participants who refuse surgery or have residual disease. Disease-free survival is defined as the time from radical cystectomy to the earliest of disease recurrence after radical cystectomy or death due to any cause, with rates evaluated at 18 and 24 months. Overall survival is defined as the time from first neoadjuvant durvalumab plus ddMVAC treatment until death due to any cause, with the primary measure of interest being the 12-month rate.

Pathologic response will be assessed by local pathology review of specimens obtained via radical cystectomy. Pathologic complete response is defined as pathologic staging of T0N0M0. Pathologic downstaging is defined as pathologic staging of < P2. Participants who do not undergo radical cystectomy will be counted as failures for the pathologic complete response assessment.