Dr Necchi on Molecular Data With Perioperative Sacituzumab Govitecan Plus Pembrolizumab in MIBC

"The story [of these data are] pretty consistent [with] the classical biomarker associated with immunotherapy: higher tumor mutational burden portended higher responses and higher clinical responses."

Andrea Necchi, MD, an associate professor at Vita-Salute Raffaele University and the head of genitourinary medical oncology at IRCCS San Raffaele Hospital and Scientific Institute in Italy, discusses initial molecular profiling data from the phase 2 SURE-02 trial (NCT05535218), which evaluated perioperative sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) in cisplatin-ineligible muscle-invasive bladder cancer (MIBC).

Data presented during the 2025 ASCO Annual Meeting showed that neoadjuvant sacituzumab govitecan plus pembrolizumab, followed by response-adapted bladder sparing and adjuvant pembrolizumab, produced a clinical complete response (cCR) rate of 44.4% (n=16; 95% CI: 27.9-61.9) with the neoadjuvant regimen, followed by response-adapted bladder sparing and adjuvant pembrolizumab. Notably, all of these patients underwent repeated transurethral resection of a bladder tumor (re-TURBT), and 55.6% achieved ypT ≤1N0-x following either radical cystectomy or bladder preservation, demonstrating a significant pathological response.

These represent the first data of their kind ever presented in this context, Necchi stated. The analysis revealed crucial insights into patient responsiveness, showing that patients with luminal subtype tumors were more likely to respond to the treatment. This observation is particularly impactful given that luminal subtypes are traditionally associated with immunotherapy resistance or poor responses, suggesting that sacituzumab govitecan could be significantly contributing to improved outcomes in this patient group, he explained. Further supporting these findings, the study found that higher levels of TROP-2 expression were associated with a flat event-free survival curve, indicating a more durable benefit in these patients, Necchi reported. He added that ARID1A mutations were observed in TROP-2. Lastly, TROP-2 expression in complete responders was notably enriched in the luminal subtype, reinforcing the importance of this molecular characteristic, he stated.

Overall, a higher tumor mutational burden (TMB) correlated with superior responses and higher clinical responses, providing a familiar marker for predicting treatment success, Necchi asserted. These initial biomarker findings offer crucial guidance for understanding patient selection and potentially predicting response in MIBC, Necchi concluded.