Sacituzumab govitecan/pembrolizumab achieves promising CR rate in MIBC

Data from the phase 2 SURE-02 trial (NCT05535218) have been published in Lancet Oncology, showing encouraging outcomes with a perioperative regimen of sacituzumab govitecan (Trodelvy) plus pembrolizumab (Keytruda) in patients with muscle-invasive bladder cancer (MIBC) who are ineligible for or decline cisplatin-based neoadjuvant chemotherapy.¹

The findings, previously reported in abstract form at the 2025 American Society of Clinical Oncology Annual Meeting, showed a clinical complete response (cCR) rate of 39% (19 of 49) following neoadjuvant therapy, suggesting the potential for bladder preservation in a subset of patients.

“The SURE-02 trial pioneered the use of an ADC/IO combination as a perioperative therapy in patients with MIBC who were ineligible for or refused cisplatin-based neoadjuvant chemotherapy,” explained lead author Andrea Necchi, MD, in correspondence with Urology Times®. “In this single-arm trial conducted in 49 patients, 39% of them achieved a [cCR] after neoadjuvant therapy and were able to avoid radical cystectomy while proceeding to the maintenance pembrolizumab therapy for up to 12 months.”

Trial overview

SURE-02 was conducted at IRCCS San Raffaele Hospital in Milan, Italy. Investigators enrolled adults with newly diagnosed cT2-T3bN0M0 MIBC and an ECOG performance status of 0 or 1. Participants were either ineligible for cisplatin-based neoadjuvant chemotherapy or declined it.

Patients received 4 cycles of pembrolizumab 200 mg intravenously on day 1 plus sacituzumab govitecan 7.5 mg/kg intravenously on days 1 and 8 of a 21-day cycle. Patients then underwent radical cystectomy or, if they declined surgery after multidisciplinary review, repeat transurethral resection of bladder tumor (re-TURBT). Thirteen additional cycles of pembrolizumab were planned postoperatively.

Between October 2023 and February 2025, 49 patients were enrolled and evaluable. The median age was 66 years. Among all patients, 16% were women, and 43% had centrally confirmed variant histology.

Efficacy data

After a median follow-up of 14 months (IQR, 8 to 18), 19 patients achieved cCR (39%; 95% CI, 25% to 54%), defined by negative imaging and no viable tumor at re-TURBT. Two patients later developed intravesical relapse, but no distant metastatic relapses were reported among patients with cCR at the time of analysis.

RELATED: Perioperative sacituzumab govitecan/pembro yields compelling CR rate in MIBC

The 12-month event-free survival (EFS) in the intent-to-treat population was 71% (95% CI, 57%-89%). The estimated 12-month metastasis-free survival was 74% (95% CI, 60%-91%), and the 12-month bladder-intact EFS was 38% (95% CI, 25%-59%).

Investigators noted that all patients who underwent re-TURBT plus maintenance pembrolizumab in the bladder-sparing pathway were alive without events, aside from delayed cystectomies, at data cutoff. This translated to a reported 12-month metastasis-free survival rate of 100% in that subgroup. The 12-month EFS and bladder-intact EFS in this subgroup were each 91% (95% CI, 75%-100%).

Exploratory correlative analyses suggested higher cCR rates in luminal subtype tumors, with a reported cCR rate of 57% in patients with a luminal subtype vs 33% for those with nonluminal subtypes (P = .073). Investigators also observed enrichment of ERBB2 alterations (42% vs 14%; P = .55) among responders.

Safety findings

Grade 3 treatment-related adverse events occurred in 16% of patients. Diarrhea was the most common grade 3 toxicity (8%). No grade 4 or higher treatment-related adverse events or treatment-related deaths were reported. Serious treatment-related adverse events occurred in 3 patients (6%), including bullous pemphigoid in 2 patients and colitis in 1 patient.

The reduced sacituzumab govitecan dose used in SURE-02 (7.5 mg/kg) reflected lessons from the earlier SURE-01 neoadjuvant monotherapy study (NCT05226117), in which the standard 10 mg/kg dose was associated with substantial hematologic and gastrointestinal toxicity.

Interpretations and next steps

The authors acknowledged several limitations of the trial, including the single-center and single-arm study design, the small sample size, and the relatively short follow-up period. The authors also noted that the high proportion of patients refusing chemotherapy and the absence of patients with an ECOG performance status of 2 could limit cross-trial comparisons.

Altogether, these findings add to ongoing work looking at systemic therapy–driven organ preservation.

Necchi concluded, “The study provides additional evidence on 2 important topics of today’s research in MIBC: [One, treating] patients with novel systemic therapy and a conservative surgical approach is feasible and safe whenever the patients achieve a [cCR], rigorously defined with the combination of advanced imaging (MRI) and a radical re-TURBT (not only a biopsy). [Second,] TROP2 is a reliable target in MIBC and could provide alternative options, in combination with an immune-checkpoint inhibitor, other than the EV-pembro [enfortumab vedotin and pembrolizumab] combination. The clinical CR enrichment in luminal subtype tumors represents proof for further biomarker research in the ADC context.”

REFERENCE

1. Necchi A, Maiorano BA, de 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. 2026;27(4):442-451. doi:10.1016/S1470-2045(26)00050-1