Neoadjuvant Sacituzumab Govitecan Plus Pembrolizumab Followed By Pembrolizumab Maintenance Demonstrates Efficacy in MIBC

Neoadjuvant sacituzumab govitecan-hziy (Trodelvy) in combination with pembrolizumab (Keytruda) followed by response-adapted bladder sparing and adjuvant pembrolizumab displayed encouraging activity in patients with muscle-invasive bladder cancer (MIBC), according to findings from the phase 2 SURE-02 trial (NCT05535218) presented during the 2025 ASCO Annual Meeting.1

Initial findings from SURE-02 revealed that patients with MIBC in the intention-to-treat (ITT) population (n = 36) achieved a clinical complete response (cCR) rate of 44.4% (95% CI, 27.9%-61.9%). Moreover, the ypT ≤ 1N0-x rate was 55.6%.

“The cCR rate of 44.4% was promising and [importantly], all of these patients were able to keep their bladder,” Andrea Necchi, MD, said in an interview with OncLive®. “In particular, [patients with] luminal subtype tumors were more likely to respond to treatment. Luminal subtypes are classically associated with immunotherapy resistance or [a poor response to] immunotherapy.”

Necchi is an associate professor of Oncology at Vita-Salute San Raffaele University and director of Genitourinary Medical Oncology at IRCCS San Raffaele Hospital and Scientific Institute in Milan, Italy.

Examining the SURE-02 Study Design and Baseline Characteristics

SURE-02 was an Italian, open-label, single-arm study that enrolled adult patients with MIBC who could not receive or refused cisplatin-based chemotherapy.2 Patients needed to have an ECOG performance status of 0 or 1, adequate hematologic counts and hepatic function, a creatine clearance of at least 30 mL/min as assessed by the Cockcroft-Gault equation, predominant urothelial carcinoma histology, be eligible for radical cystectomy, and clinical stage T2 to T3 N0M0 MIBC as assessed by CT plus PET scan or CT scan plus pelvic MRI.

All patients received intravenous (IV) sacituzumab govitecan at 7.5 mg/kg on days 1 and 8 plus IV pembrolizumab at 200 mg every 3 weeks for 4 cycles. Patients then underwent radical cystectomy or a restage transurethral resection of bladder tumor (TURBT) followed by adjuvant or maintenance IV pembrolizumab at 200 mg every 3 weeks for 13 cycles. The follow-up period was 24 months occurring at every 12 weeks following surgery.

The primary end point was cCR rate assessed at 36 months.1,2 Secondary end points included pathological response rate, bladder-intact event-free survival (EFS) rate, metastasis-free survival (MFS), overall survival, and safety. Biomarkers of response, changes in biomarker expression, and microbiome data in urine and feces were evaluated as exploratory end points.

At baseline, the median age in the ITT population was 64 years (IQR, 61-71) and all patients were White.1 Most patients were male (77.8%), refused neoadjuvant chemotherapy (63.9%), refused chemoradiotherapy (80.6%), had residual disease (72.2%), and had stage c T2N0 disease (69.4%). Urothelial carcinoma with variant histology was present in 38.9% of patients and 11.1% underwent prior intravesical therapy.

Additional Efficacy Data and Safety Findings

At a median follow-up of 10 months (IQR, 7.3-13), the 12-month EFS rate was 71.3% (95% CI, 55.7%-91.2%) and the 12-month MFS rate was 84.2% (95% CI, 72%-98.5%). The 12-month bladder-intact EFS rates among patients who achieved a cCR (n = 16) and in those who underwent TURBT (n = 23) were 100% and 74% (95% CI, 54.8%-99%), respectively.

In the safety population (n = 49), any-grade treatment-related adverse effects (TRAEs) occurred at a rate of 97.9%. Grade 1 (85.7%), grade 2 (55.1%), and grade 3 to 4 (18.4%) TRAEs were all reported. Any-grade immune-related adverse effects (irAEs) were reported in 46.9% of patients; this was comprised of grade 1 (34.7%), grade 2 (18.4%) and grade 3 to 4 (4.1%) irAEs.

Treatment-related and non-treated–related serious adverse effects were reported in 8.2% and 10.2% of patients, respectively. Patients permanently discontinued treatment with neoadjuvant sacituzumab govitecan prior to receipt of 4 cycles due to a TRAE at a rate of 6.1%. Patients required steroid therapy at a rate of 14.3%. Notably there were no dose reductions of sacituzumab govitecan; overall, dose omissions and delays occurred at rates of 6.1% and 8.2%.

“The flexibility for bladder preservation, depending on patient preference and response to treatment, is the way to [move forward for these patients],” Necchi said. “The possibility of avoiding chemotherapy [and/or] chemoradiotherapy are good things, but we still need to learn [how to] optimize the regimen, maintenance therapy, duration of therapy, and therapy deescalation.”

Disclosures: Necchi reported employment as well as stock and other ownership interests with Bayer. He also holds consulting or advisory roles with AstraZeneca, Bicycle Therapeutics, Bristol-Myers Squibb, Catalym, Genenta Science, Gilead Sciences, Incyte, Johnson & Johnson/Janssen, Merck Serono, Merck Sharp & Dohme, Peerview, PeerVoice, Samsung Bioepis, and Seattle Genetics/Astellas. He received research funding from Bristol-Myers Squibb/Celgene, Gilead Sciences, and Merck Sharp & Dohme. He received travel, accommodations, and expenses from AstraZeneca, Gilead Sciences, Janssen, and Merck Sharp & Dohme.

References

1. Necchi A, de Jong J, Proudfoot J, et al. First results of SURE-02: a phase 2 study of neoadjuvant sacituzumab govitecan (SG) plus pembrolizumab (pembro), followed by response-adapted bladder sparing and adjuvant pembro, in patients with muscle-invasive bladder cancer (MIBC). J Clin Oncol. 2025;43(suppl 16):4518. doi:10.1200/JCO.2025.43.16_suppl.4518
2. Pembrolizumab-sacituzumab govitecan combination to treat high-risk, localized bladder cancer (SURE-02). ClinicalTrials.gov. Updated April 2, 2025. Accessed August 25, 2025. https://clinicaltrials.gov/study/NCT05535218