Neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by adjuvant pembrolizumab, in patients with muscle-invasive bladder cancer (SURE-02): a single-arm, phase 2 study.

backgroundStandard-of-care treatment for muscle-invasive bladder cancer is radical cystectomy with neoadjuvant chemotherapy; however, approximately 50% of patients are ineligible for or refuse neoadjuvant chemotherapy. Neoadjuvant pembrolizumab and sacituzumab govitecan have shown activity as monotherapy in muscle-invasive bladder cancer. We aimed to evaluate the clinical activity of neoadjuvant sacituzumab govitecan plus pembrolizumab and adjuvant pembrolizumab, within a bladder-sparing approach.

methodsSURE-02 is a single-arm, phase 2 study, conducted at IRCCS San Raffaele Hospital in Milan, Italy. Eligible patients were aged 18 years or older, had an Eastern Cooperative Oncology Group performance status 0-1, were newly diagnosed with histologically confirmed muscle-invasive bladder cancer (stage cT2-T3bN0M0), were deemed ineligible for or declined cisplatin-based neoadjuvant chemotherapy, and were scheduled for radical cystectomy. Patients received four cycles of intravenous pembrolizumab 200 mg on day 1 and intravenous sacituzumab govitecan 7·5 mg/kg on day 1 and day 8, every 3 weeks, followed by radical cystectomy or redo-transurethral resection of the bladder tumour (re-TURBT; after multidisciplinary tumour board discussion in patients who refused to undergo radical cystectomy) and 13 cycles of postsurgical pembrolizumab 200 mg, every 3 weeks. The primary endpoint was the clinical complete response rate, defined as negative imaging and no viable tumour at re-TURBT in patients not undergoing radical cystectomy. Efficacy was assessed in all patients who received at least one dose of study treatment and had a baseline evaluation (intention-to-treat population). This study is registered with ClinicalTrials.gov, NCT05535218, and is active but not recruiting.

findingsBetween Oct 2, 2023, and Feb 26, 2025, 63 patients were screened, 49 patients (median age 66 years [IQR 61-71]; eight [16%] female and 41 [84%] male; 48 [98%] White and one [2%] Black) were enrolled, treated, and evaluated for safety and efficacy. 33 (67%) had a cT2 stage, 21 (43%) had a centrally confirmed variant histology. After a median follow-up of 14 months (IQR 8-18), 19 (39% [95% CI 25-54]) patients had a clinical complete response; all of whom underwent a re-TURBT. All patients with clinical complete response were metastasis-free; two patients developed an intravesical relapse. Grade 3 treatment-related adverse-events occurred in eight patients (16%), the most common being diarrhoea (in four [8%]). There were no treatment-related deaths. Serious treatment-related adverse events were reported in three patients (6%); bullous pemphigoid in two and colitis in one patient respectively.

interpretationPerioperative sacituzumab govitecan plus pembrolizumab revealed a promising clinical complete response rate, without the occurrence of grade 4 or higher adverse events, allowing a bladder preservation with sustained remission in approximately 40% of patients.

fundingMerck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA and Gilead Sciences.