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Neoadjuvant Sacituzumab Govitecan plus Pembrolizumab, Followed by Adjuvant Pembrolizumab, in Patients with Muscle-Invasive Bladder Cancer (SURE-02): A Single-Arm, Phase 2 Study - Beyond the Abstract

The SURE-02 trial was initially designed to address an unmet medical need represented by the perioperative therapy of patients with muscle-invasive urothelial bladder cancer (MIBC), who were ineligible for or refused standard cisplatin-based chemotherapy. The study was initially designed as a classical perioperative study for MIBC, including a neoadjuvant treatment with four courses of the combination of sacituzumab govitecan and pembrolizumab, followed by radical cystectomy and 13 cycles of adjuvant pembrolizumab.

After the initial patients enrolled, due to the amount of protocol deviations due to patients’refusal to undergo radical cystectomy after neoadjuvant therapy, the protocol underwent a substantial amendment allowing bladder preservation via a repeated transurethral resection of the bladder tumor (reTURBT) instead of cystectomy, depending on the patient's decision. The primary endpoint, which was initially planned to be the pathological complete response rate, became the clinical complete response rate (cCR), stringently defined as a negative imaging and a negative reTURBT histology, as it was recommended later at the Milan consensus meeting.1

In this study, enrolling a total of 49 patients between Oct 2023 and Feb 2025, the primary endpoint was achieved in 19 patients (38.8%). Twelve-month event-free survival (EFS) in the intention-to-treat population was 71%. After a median follow-up of 14 months, there were two intravesical relapses in the cCR group. Most noteworthy, none of the patients in the reTURBT group developed distant metastases, and there were four delayed cystectomies in this group.

The safety profile indicated that, by administering sacituzumab govitecan at the dose of 7.5 mg/Kg with primary prophylaxis for neutropenia, Grade 3 treatment-related adverse events (TRAE) were reported in 8 patients (16.3%), and there were no Grade >3 TRAEs. The safety profile attributable to pembrolizumab (i.e., immune-related TRAE) was consistent with the literature results.

Exploratory biomarker analyses focused on associations of gene expressions and genomic alterations profiling with cCR. Luminal subtype tumors showed higher cCR rates (57% versus 33% in non-Luminal). ERBB2 gene alterations and elevated HER2 gene expression were enriched in the Luminal subtype, as previously described, thus representing further putative biomarkers of response to anti-TROP2 targeting in patients with MIBC. Conversely, there were no signals of associations for TROP2 gene expression and response.

The study is the first to provide an antibody-drug conjugate (ADC) plus immune-checkpoint inhibitor approach in a bladder-sparing perioperative strategy for patients with MIBC. It supports the feasibility and safety of offering a patient-driven bladder sparing option, primarily dictated by clinical response to combined ADC and ICI treatment. This approach may enable durable tumor control while preserving the bladder in a subset of patients, representing a shift toward personalized, response-guided, and patient-driven perioperative management and organ preservation in MIBC.

SURE-02 is limited by its single-arm, single-centre design and the short follow-up duration, which prevented robust associations with survival endpoints.

These results should also be contextualized into the recent developments of perioperative enfortumab vedotin plus pembrolizumab, as well as into the development of novel anti-TROP2 ADCs in patients with urothelial carcinoma.2

Differentiating the therapeutic pathways, ideally through the use of tumor biomarkers for patient selection, will likely be one of the key strategies for the future development of systemic therapies in patients with MIBC.

The design and endpoints of clinical trials similar to SURE-02, aimed at registration purposes, remain a matter of intense debate in the genitourinary oncology community, and represent one of the most intriguing challenges of clinical research that is primarily dictated by the patients.

Written by: Chiara Mercinelli,1,2 and Andrea Necchi1,2

  1. Department of Medical Oncology, IRCCS San Raffaele Hospital, Comprehensive Cancer Center
  2. Vita-Salute San Raffaele University, Milan, Italy
References:

  1. Necchi A, Galsky MD, Dizman N, et al. End Points for the Next-Generation Bladder-Sparing Perioperative Trials for Patients With Muscle-Invasive Bladder Cancer. J Clin Oncol. 2025 Nov 10;43(32):3536-3544.
  2. Vulsteke C, Adra N, Danchaivijitr P, et al. Perioperative Enfortumab Vedotin and Pembrolizumab in Bladder Cancer. N Engl J Med. 2026 Feb 18. doi: 10.1056/NEJMoa2511674. Online ahead of print.
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