Sacituzumab govitecan showed clinical activity as neoadjuvant therapy in patients with muscle-invasive bladder cancer who were ineligible for, or refused, cisplatin-based neoadjuvant chemotherapy, according to primary results from the phase 2 SURE-01 trial.
Patients with muscle-invasive bladder cancer who cannot receive cisplatin-based neoadjuvant chemotherapy have limited systemic treatment options before radical cystectomy. SURE-01 evaluated whether sacituzumab govitecan, an anti-TROP2 antibody-drug conjugate, could provide a neoadjuvant treatment approach for this population.
The study reported evidence of activity with sacituzumab govitecan, particularly in a post hoc analysis that considered pathologic findings from both radical cystectomy and repeat transurethral resection.
The study was published on May 31, 2026, in the Journal of Clinical Oncology.
Title: “Neoadjuvant Sacituzumab Govitecan in Patients With Muscle-Invasive Bladder Cancer: Primary Results of the SURE-01 Trial.”
Authors: 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, and Francesco Montorsi.
Read more about Sacituzumab govitecan (Trodelvy) Updates on OncoDaily.
Study Design
SURE-01 was a phase 2 study conducted at IRCCS San Raffaele Hospital in Milan, Italy.
Eligible patients were adults with histologically confirmed cT2-T4aN0M0 muscle-invasive bladder cancer, ECOG performance status 0–1, and were scheduled for radical cystectomy. Patients were either ineligible for cisplatin-based neoadjuvant chemotherapy or refused it.
Patients initially received sacituzumab govitecan 10 mg/kg on day 1 and day 8 every 3 weeks for four cycles before radical cystectomy. After the first eight patients were enrolled, the study was temporarily stopped because of treatment-related adverse events and two deaths, one of which was treatment-related. The protocol was then amended to reduce the sacituzumab govitecan dose to 7.5 mg/kg and to add primary prophylaxis for neutropenia.
The primary endpoint was pathologic complete response, defined as ypT0N0 after radical cystectomy. Secondary endpoints included pathologic downstaging, event-free survival, overall survival, and safety. Biomarker analyses were also performed on baseline tumor samples.
Patient Population
A total of 44 patients were treated and included in the efficacy and safety analysis. The median age was 72 years. All patients had ECOG performance status 0. Overall, 59.1% had cT3-4 disease, including 20.5% with cT4 disease. Variant histology was present in 45.5% of patients.
Among the reasons for not receiving cisplatin-based chemotherapy, 52.3% were unfit because of glomerular filtration rate below 60 mL/min, 2.3% were unfit because of preexisting hypoacusis, and 45.4% refused cisplatin.
Efficacy Results
In the intention-to-treat population, the protocol-defined ypT0N0 response rate was 9.1% with a 95% CI of 2.5 to 21.7. When responses from radical cystectomy and repeat transurethral resection of bladder tumor were considered together in a post hoc analysis, the ypT0N0-x response rate was 29.5% with a 95% CI of 16.7 to 45.2. Pathologic downstaging to ypT≤1N0-x was observed in 34.1% of patients.
After a median follow-up of 22 months, the 24-month event-free survival rate was 71.4%, with a 95% CI of 58.0 to 87.8. The 24-month overall survival rate was 80.2%, with a 95% CI of 67.7 to 95.0. Among patients who achieved ypT0, the 24-month event-free survival rate was 100%. In the remaining patients, the 24-month event-free survival rate was 61.3%.
Of note, 14 patients refused radical cystectomy after neoadjuvant therapy. Twelve underwent repeat transurethral resection of the bladder tumor, while two had imaging assessment showing complete response without biopsy because of patient refusal. At the time of analysis, no intravesical recurrences were reported among patients who declined radical cystectomy.
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Safety
Safety findings differed substantially between the initial 10 mg/kg cohort and the reduced-dose 7.5 mg/kg cohort. Among the first eight patients treated at 10 mg/kg, grade 3–4 neutropenia occurred in 75% and grade 3–4 diarrhea occurred in 50%. Two deaths occurred in this initial cohort, including one treatment-related death from septic shock.
After the protocol amendment, 36 patients received sacituzumab govitecan at 7.5 mg/kg with primary neutropenia prophylaxis. In this cohort, grade 3–4 neutropenia occurred in 5.6% and grade 3–4 diarrhea occurred in 2.8%. Two patients discontinued sacituzumab govitecan because of treatment-related adverse events, and one patient required dose reduction to 5 mg/kg.
The reduced dose was associated with a lower rate of severe treatment-related adverse events while preserving evidence of clinical activity.
Biomarker Findings
Biomarker analyses suggested potential molecular features associated with response and outcome. ypT0 responses were enriched in nonluminal tumor subtypes, occurring in 46% of nonluminal tumors compared with 14% of luminal tumors.
TROP2 expression was not significantly associated with ypT0 response or event-free survival. In contrast, lower TOP1 expression was associated with longer event-free survival. Patients in the lowest tertile of TOP1 expression had a 24-month event-free survival rate of 100%. Lower FGFR3 activity signature scores were also associated with longer event-free survival. The biomarker findings were exploratory and require prospective validation.
Conclusion
SURE-01 provides early evidence that neoadjuvant sacituzumab govitecan has activity in muscle-invasive bladder cancer among patients who are ineligible for or refuse cisplatin-based neoadjuvant chemotherapy.
The study did not meet its protocol-defined primary endpoint based on ypT0N0 after radical cystectomy alone, and interpretation is limited by protocol deviations, including refusal of radical cystectomy in several patients. However, the overall ypT0N0-x response rate of 29.5%, the 24-month event-free survival rate of 71.4%, and the biomarker signals observed with nonluminal subtypes and lower TOP1 expression support further investigation of anti-TROP2 antibody-drug conjugates in this setting.
The reduced sacituzumab govitecan dose of 7.5 mg/kg with neutropenia prophylaxis appeared more manageable than the initial 10 mg/kg dose while preserving evidence of activity.
The full article is available in the Journal of Clinical Oncology.