SURE-01/02: Perioperative Sacituzumab Govitecan for Patients With MIBC

Neoadjuvant sacituzumab govitecan (SG) demonstrated promising clinical activity in patients with muscle invasive bladder cancer (MIBC) and may help avoid radical cystectomy (RC), according to interim results of the SURE-01 and SURE-02 trials presented as a late-breaking abstract at the 2024 American Society of Clinical Oncology Annual Meeting.

SG is US Food and Drug Administration-approved to treat locally advanced or metastatic urothelial carcinoma. Antonio Cigliola, PhD, of IRCCS San Raffaele Hospital, and colleagues designed the multicohort, open-label, phase 2 SURE study to evaluate neoadjuvant SG (SURE-01) or neoadjuvant SG plus pembrolizumab followed by adjuvant pembrolizumab (SURE-02) in patients with MIBC. The trial included a flexible design to allow for a bladder-sparing approach.

Patients with cT2-4N0M0 MIBC who were ineligible for cisplatin-based neoadjuvant chemotherapy were given 4 cycles of neoadjuvant SG (10 mg/kg IV on days 1 and 8, Q3W) followed by RC. Those who experienced clinical complete response (cCR) who refused RC were offered redo transurethral resection of the bladder tumor (reTURBT) followed by observation.

The primary end point of the study is to assess the proportion of ypT0N0, and secondary end points include event-free survival (EFS), cCR rate, and OS.

From March 2022 to November 2023, a total of 21 patients were enrolled in the study, and after the initial 8 patients were treated, the SG dosage was amended to 7.5 mg/kg due to observed grade 5 treatment-related adverse events (TRAEs). All patients received at least 1 cycle of SG, and grade 3 or higher TRAEs occurred in 9 patients, researchers noted. Toxicity was unrelated to UGT1A1 polymorphism, they added.

Dr. Cigliola and colleagues found that 10 patients experienced a cCR. Among the 16 patients who were evaluable for final response at treatment completion, only 1 patient had disease progression and started palliative therapy, and 2 patients did not undergo RC due to TRAEs.

Thirteen patients have since undergone surgery (RC, n=10; reTURBT, n=3), and a ypT0N0 response was achieved in 6 (37.5%) of the evaluable patients. Notably, 7 (43.7%) patients had a ypT≤1N0 response.

Furthermore, all patients with residual disease were ctDNA-negative after RC. Tumor samples from patients with cCR were enriched in ARID1A (40% vs 9%, respectively) and BRCA1/2 (30% vs 18%, respectively) mutations compared with noncomplete responders, and tumor sampled from noncomplete responders were enriched in ERBB2 (44% vs 10%, respectively) mutations compared with those who experienced cCR.

“Observed ypT0N0 responses after neoadjuvant SG showed promising activity in patients with MIBC who have a high unmet need, with a potential to avoid RC,” Dr. Cigliola concluded. “Reduced dose of SG is feasible, and the data support the ongoing SURE studies in MIBC.”