IBCN 2023: SURE-01: Interim Results of a Phase 2 Study of Neoadjuvant Sacituzumab Govitecan, Followed by Radical Cystectomy, for Patients with Muscle-Invasive Bladder Cancer

(UroToday.com) For patients with muscle invasive bladder cancer (MIBC) who cannot receive or refuse cisplatin-based chemotherapy, there is no standard-of-care neoadjuvant therapy. SG is an antibody-drug conjugate (ADC) targeting Trop-2, with SN-38 as a payload. In SURE-01 (NCT05226117) they aimed to evaluate the efficacy of neoadjuvant sacituzumab govitecan (SG) before radical cystectomy.

In SURE-01, patients have a histopathologically-confirmed predominant urothelial carcinoma (UC), a clinical stage T2-T4N0M0 MIBC, and should be ineligible or refuse to receive cisplatin-based chemotherapy. Patients receive 4 cycles of 10 mg/Kg SG IV, on days 1, 8, of each 21-day cycle, before radical cystectomy. After surgery, patients are managed according to standard practice. The primary endpoint is the proportion of ypT0N0. The assumptions include a ypT0N0 20% as H0 and 45% as H1 in a single-stage design, accounting for a total of 56 patients.

From 03-06/2022, 8 patients were enrolled. Median age was 77y, 4 patients had a cT3-4N0, 4 a cT2N0. Four patients (50%) had a mixed variant histology. All patients received at least 1 cycle of SG: Grade 3-4 neutropenia was seen in 6/8 pts (75%), Grade 3-4 diarrhea in 4/8 (50%). Two patients (25%) had treatment discontinuation after C1D8 and died: one due to treatment-related sepsis and diarrhea, one due to complications following a treatment-related sepsis. The remaining pts had dose reduction to 75% since C2D1. Toxicity was unrelated to UGT1A1 polymorphism. 3/6 patients (50%) receiving radical cystectomy achieved a ypT0N0 response, 2 patients ypT3N0, one an ypT3N1. All patients with a residual disease revealed a ctDNA-negative Signatera test post-radical cystectomy. All 6 patients are currently alive without relapse.

In summary, based on interim safety results, SURE-01 was amended and a dose-reduction to 7.5 mg/Kg SG is now administered since C1D1, added to primary prophylaxis with GCSF. Encouraging preliminary efficacy data with SG monotherapy were seen.

Presented by: Antonio Cigliola, Department of Medical Oncology, IRCCS San Raffaele Hospital, Milan, Italy

Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network (IBCN) Annual Meeting, September 29-30, 2023, Montreal, Canada