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

BACKGROUND

Standard-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.

METHODS

SURE-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.

FINDINGS: Between 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.

INTERPRETATION: Perioperative 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.

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