Neoadjuvant and adjuvant enfortumab vedotin (EV) plus pembrolizumab (pembro) for participants with muscle-invasive bladder cancer (MIBC) who are eligible for cisplatin: Randomized, open-label, phase 3 KEYNOTE-B15 study.

Abstract

Background: Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with a high risk of progression, representing a major therapeutic challenge. Adaptive bladder-sparing strategies, which rely on restaging to guide treatment decisions, are being adopted for MIBC management, demonstrating effective disease control while avoiding radical cystectomy (RC)-associated morbidities. This study aims to evaluate a bladder-sparing approach using sasanlimab, a PD-1 inhibitor, as maintenance treatment in patients who achieve a clinical response following neoadjuvant cisplatin-based chemotherapy. Methods: The SASAN-SPARING (HM-8788561) trial is a single-arm, multicentre, phase 2 clinical study that evaluates the efficacy and safety of sasanlimab as maintenance treatment following neoadjuvant cisplatin-based chemotherapy in patients (aged ≥18 years) with treatment-naïve, localized MIBC who are candidates to receive neoadjuvant chemotherapy followed by RC. The study follows an adaptive treatment strategy, where patients receive four cycles of neoadjuvant chemotherapy consisting of cisplatin (70 mg/m2, day 1), and gemcitabine (1000 mg/m2, days 1 and 8) every three weeks. Following chemotherapy, patients are restaged, those achieving a clinical response (defined as cT0/Ta/T1/Tis, normal cytology, and negative imaging) are eligible for bladder preservation and receive sasanlimab (300 mg) subcutaneously every 4 weeks for up to 12 cycles, whereas non-responders (≥cT2) undergo RC. During maintenance, patients are restaged every 12 weeks, in case of progression or loss of response, RC may be considered at the physician’s discretion. The primary endpoint is the bladder-intact overall survival (biOS), at 12 months after the first dose of sasanlimab. Secondary endpoints include clinical response rate, disease-free survival, overall survival, safety, and patient-reported outcomes. The study integrates a comprehensive biomarker program, including whole-genome sequencing of tumour tissue and plasma, the use of circulating tumor DNA (ctDNA) in plasma and urine for tumour assessment and molecular dynamics, and gut microbiome profiling. Correlative analyses aim to refine patient selection and generate hypotheses for future adaptive treatment strategies. A total of 70 patients are planned for enrollment, assuming a 12-month biOS of 81% (H0) and an increase with sasanlimab up to 93% (H1) (one-arm survival test; α = 0.05, β= 0.8). Recruitment started in December 2024, and at the data cutoff, October 2025, 40 patients had been enrolled, of whom 13 initiated sasanlimab maintenance therapy. Clinical trial information: NCT06623162.