Sacituzumab Govitecan Plus Pembrolizumab Enables Bladder Preservation in Muscle-Invasive Bladder Cancer

Clinical Summary:

• Design/Population: The single-arm, phase 2 SURE-02 study evaluated perioperative sacituzumab govitecan plus pembrolizumab in 49 patients with cT2-T3bN0M0 muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based neoadjuvant chemotherapy. Patients achieving a clinical complete response could undergo repeat transurethral resection of the bladder tumor (re-TURBT) as part of a bladder-preserving strategy followed by adjuvant pembrolizumab.

• Key Outcomes: A clinical complete response was achieved in 39% of patients, allowing bladder preservation in all responders. After a median follow-up of 14 months, all patients with a clinical complete response remained metastasis-free, treatment-related adverse events were manageable, and no grade 4 or 5 treatment-related toxicities were observed.

• Clinical Relevance: These findings support perioperative sacituzumab govitecan plus pembrolizumab as a promising bladder-preserving strategy for selected patients with muscle-invasive bladder cancer who are unable or unwilling to receive cisplatin-based neoadjuvant chemotherapy.

Andrea Necchi, MD, San Raffaele Hospital, Milan, Italy, discusses results from the phase 2 SURE-02 trial evaluating perioperative sacituzumab govitecan plus pembrolizumab in patients with muscle-invasive bladder cancer who were ineligible for or declined cisplatin-based neoadjuvant chemotherapy.

The study demonstrated that nearly 40% of patients achieved a clinical complete response, enabling bladder preservation with sustained remission and no metastatic recurrences among responders during follow-up. These findings support further investigation of antibody-drug conjugate–based, response-adapted bladder preservation strategies and the identification of biomarkers to better select patients most likely to benefit.

Transcript: 

Hello, I'm Andrea Necchi. I'm a medical oncologist and director of GU medical oncology at San Raffaele Hospital in Milan, Italy, and associate professor of oncology at Vita-Salute San Raffaele University in Milan, Italy. What I'm presenting today are the top-line results of our SURE-02 study.

SURE-02 is a perioperative study employing a three-period treatment strategy: neoadjuvant therapy with the combination of the anti-TROP2 antibody-drug conjugate sacituzumab govitecan plus pembrolizumab, followed by surgery, and then followed by adjuvant pembrolizumab in patients with muscle-invasive bladder cancer, cT2 to cT3b, N0, M0, with pure or predominant urothelial carcinoma histology.

The study was initially conceived as a classical perioperative study. Then, after the initial protocol deviations due to patients refusing cystectomy based on the deep response after neoadjuvant therapy, the study was amended to include the possibility for patients to undergo re-TURBT, so to skip radical cystectomy if they responded well or refused to undergo radical cystectomy after completing the neoadjuvant treatment.

The study was actually amended to a classical response-adapted or patient-driven bladder-sparing approach, with neoadjuvant therapy consisting of sacituzumab govitecan plus pembrolizumab, followed by the patient's decision to undergo either radical cystectomy or a re-TURBT bladder-sparing approach, and then, in any case, adjuvant pembrolizumab treatment for up to one year.

The study enrolled a total of 49 patients. Overall, the clinical complete response rate—that is, the proportion of patients who achieved negative imaging, negative cystoscopy, negative biopsy, and were able to avoid cystectomy—was approximately 39%.

Most interestingly, in the intention-to-treat population, the event-free survival—and by event-free survival I mean all types of relapse, including possible intravesical high-grade non–muscle-invasive relapses—was projected to be 71% at one year. It was as high as 90% in those patients who achieved a clinical complete response with treatment.

There was also an interesting finding with regard to biomarkers. The study was enriched with biomarker analyses, including next-generation sequencing and transcriptomic analyses performed on the baseline TURBT specimens. These showed that luminal subtype tumors benefited the most in terms of clinical response.There was an enrichment of clinical complete responses among patients with luminal subtype tumors. There was no signal suggesting an association between benefit and biomarkers such as TROP2 expression or PD-L1 expression.

Overall, this study is the first of its kind to evaluate a response-adapted bladder-sparing strategy in patients with muscle-invasive bladder cancer in the context of an antibody-drug conjugate plus immunotherapy approach. We are continuing to investigate biomarkers for patient selection in order to increase the proportion of patients who achieve a complete response to treatment. But this study is, of course, the first of its kind and highlights the possibility and the suitability of TROP2 as a therapeutic target in patients with muscle-invasive bladder cancer.

Source: 

Necchi A, Maiorano BA, Jong JJ, et al. Neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by adjuvant pembrolizumab, in patients with muscle-invasive bladder cancer (SURE-02): A single-arm, phase 2 study. Lancet Oncol. Published online: February 27, 2026. doi:1 0.1016/S1470-2045(26)00050-1