Dr Necchi on the Design of the Phase 2 SURE-02 Study Assessing Pembrolizumab/Sacituzumab Govitecan in Muscle-Invasive Bladder Cancer

“SURE-02 was built on the background of the studies we have performed before [in patients with] muscle-invasive bladder cancer, looking at the activity of pembrolizumab monotherapy in the PURE-01 study, and sacituzumab govitecan monotherapy in the SURE-01 study.”

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, discussed the design of the phase 2 SURE-02 trial (NCT05535218), which evaluated the efficacy and safety of sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) in patients with muscle-invasive bladder cancer (MIBC).

The design of SURE-02 was built based on the background of 2 previous studies, including the phase 2 PURE-01 (NCT02736266) and SURE-01 (NCT05226117) studies, Necchi began. Of note, the PURE-01 study assessed neoadjuvant pembrolizumab before cystectomy in patients with MIBC; SURE-01 investigated neoadjuvant sacituzumab govitecan before radical cystectomy for the treatment of patients with MIBC who cannot or refuse to receive cisplatin-based chemotherapy.

Based on the 2 previous studies, Necchi noted that the natural direction for SURE-02 was to combine pembrolizumab with sacituzumab govitecan. Originally, SURE-02 aimed to be a perioperative study, which included a neoadjuvant combination of sacituzumab govitecan, followed by cystectomy, and subsequent maintenance or adjuvant pembrolizumab, he explained. However, after trial initiation, investigators realized a protocol deviation was needed, as the majority of patients on the study were not achieving a deep response after receiving neoadjuvant therapy, which emphasized the need to reevaluate whether patients needed to undergo radical cystectomy, he asserted. Therefore, based on the results of the reevaluation and patient preference, the study was amended to allow a multidisciplinary discussion following the neoadjuvant treatment portion of the study to allow the bladder to remain intact during treatment, which depended on patients’ responses to treatment and their preferences, he stated. Based on the changes made to the design of SURE-02, investigators shifted the focus away from pathologic complete response as the primary end point and instead focused on the clinical complete response, Necchi concluded.