To evaluate neoadjuvant sacituzumab govitecan (SG), followed by radical cystectomy (RC), in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for/refuse neoadjuvant chemotherapy (NAC). We report the results of the primary analysis and biomarker analyses of the phase II SURE-01 trial (ClinicalTrials.gov identifier: NCT05226117).
Patients were age 18 years and older, had Eastern Cooperative Oncology Group performance status 0-1, had histologically confirmed cT2-T4aN0M0 MIBC, were ineligible/refusing NAC, and were scheduled for RC received four cycles of SG 10 mg/kg on day 1 and day 8, once every 3 weeks, followed by RC. The primary outcome measure was the pathologic complete response (pT0N0) rate. Transcriptome-wide analyses and comprehensive genomic profiling assays were performed on baseline tumor samples.
From March 2022 to July 2025, 44 patients were treated and efficacy evaluable. After the initial eight patients enrolled, the protocol was amended with a SG dose of 7.5 mg/kg, with primary prophylaxis for neutropenia, due to the occurrence of two deaths (one treatment-related). Subsequent grade 3-4 treatment-related adverse-events occurred in 5 patients (13.9%). Twenty-six patients (59.1%) had a cT3-4 stage and 20 (45.5%) had a variant histology. Fourteen patients (31.8%) refused to undergo RC, accounting for 12 repeating a transurethral resection of the bladder tumor and two undergoing active surveillance. The median follow-up was 22 months (IQR, 15-26). In the intention-to-treat population, although the protocol-defined ypT0N0 rate was 9.1% (95% CI, 2.5 to 21.7), the overall ypT0N0-x rate was 29.5% (95% CI, 16.7 to 45.2), with an enrichment of ypT0 responses in nonluminal subtypes (46% v 14% of luminal). The 24-month event-free survival (EFS) rate was 71.4% (95% CI, 58 to 87.8), with longer EFS for participants with lower TOP1-expressing tumors.
Neoadjuvant SG, at the reduced dose of 7.5 mg/kg, was active with a manageable safety profile, corroborating TROP2 as a suitable target for MIBC.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2026 May 31 [Epub ahead of print]
Andrea Necchi, Joep J de Jong, Brigida A Maiorano, James A Proudfoot, Giuseppe Basile, Antonio Cigliola, Chiara Mercinelli, Valentina Tateo, Michela Piacentini, Emanuele Crupi, Giovanni L Pastorino, Gaia Latini, Enrico Tomasi, Elai Davicioni, Marco Moschini, Giorgio Brembilla, Maurizio Colecchia, Francesco de Cobelli, Jeffrey S Ross, Russell Madison, Candice Francheska B Tambaoan, Alberto Briganti, Francesco Montorsi
Department of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy., Department of Urology, Erasmus University Medical Center, Rotterdam, the Netherlands., Veracyte Inc, San Francisco, CA., Department of Urology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy., Pharmacy Unit, IRCCS San Raffaele Hospital, Milan, Italy., Department of Radiology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy., Department of Pathology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center, Milan, Italy., Vita-Salute San Raffaele University, Milan, Italy., Departments of Pathology, Medicine (Oncology), and Urology, Upstate Medical University, Syracuse, NY., Foundation Medicine, Inc, Boston, MA.