First survival outcomes and biomarker results of SURE-01: Neoadjuvant sacituzumab govitecan (SG) monotherapy, followed by radical cystectomy (RC), in patients with muscle-invasive urothelial bladder cancer (MIBC).

Abstract

4591 Background: Standard of care for MIBC is RC with neoadjuvant chemotherapy (NAC), but ~50% of pts are ineligible for NAC and 5y survival for RC alone is ≤50%. SG is an antibody-drug conjugate composed of an anti-trophoblast cell surface antigen 2 (Trop-2) antibody coupled to SN-38 (a topoisomerase-I inhibitor). SURE-01 (NCT05226117) is an ongoing study testing neoadjuvant SG before RC. Preliminary pathological response rates suggested activity (Cigliola et al., ASCO 2024). Here, we report first results on survival and biomarkers. Methods: Pts age ≥18 y, ECOG PS 0-1, with histologically confirmed cT2-T4N0M0 MIBC, ineligible/refusing NAC and scheduled for RC, received 4 cycles of SG 7.5 mg/kg intravenously (reduced dose in protocol amendment 1) on days 1 and 8, Q3W, followed by RC. Primary study endpoint was the proportion of ypT0N0. Secondary endpoints included event-free survival (EFS), relapse-free survival (RFS) post-surgery, overall survival (OS), and safety. EFS included relapse/progression, inability/unwillingness to undergo RC in pts with residual disease, and death. Pts refusing RC with evidence of ypT0 response were censored. Decipher Bladder (Veracyte, San Diego, CA) was used on primary TURBT tissue for transcriptome-wide analyses. Signatera was used for ctDNA assessment. Results: From 03/22 to 01/25, 37 pts were enrolled and 33 were efficacy-evaluable. Median age was 71y and 16 pts (48.5%) had cT3-4N0 stage. Twelve pts (36.4%) had mixed variant histology. Grade > 3 treatment-related adverse events (TRAE) occurred in 9 pts (27.3%), including one Grade 5 (at 10mg/Kg dose). Nine pts (27.3%) refused RC and were assessed with a reTURBT. The ypT0N0-x rate was 36.4% (12/33, 95%CI: 20.4-54.9%) and ypT < 1N0-x rate was 39.4% (13/33). 8/10 pts with a high-risk disease at RC had ctDNA-negative status post-RC. Median follow-up was 14 (range 10-17) months. For the intention-to-treat (ITT) population, 12m-EFS was 78.8% (95%CI: 66-94%). 12m-Relapse-free survival (RFS) post-RC/reTURBT was 100% in pts with an ypT < 1N0-x response vs 81.2% in pts with an ypT2-4N0 or ypTanyN1-3 response. Transcriptome-wide data for 27 pts revealed 12m-RFS rate of 100% in N = 8 Infiltrated-Luminal (IL), 86% in N = 7 Claudin Low, 83% in N = 6 Basal and 75% in N = 6 Luminal cases (Log-rank, p = 0.24), with consistent associations found for ypT0 response (IL: 71% ypT0 rate). Lower ( < median) TOP1 gene expression (N = 14) was associated with 100% 12m-RFS rate (Log-rank, p = 0.05). Trop-2 gene expression did not associate to neither ypT response (p = 0.69) nor RFS. Conclusions: SURE-01 revealed compelling survival outcomes. While survival estimates or transcriptome results were not overtly associated with pathological response (interim endpoint), molecular subtypes and TOP1 gene expression may be putative biomarkers of SG efficacy. Clinical trial information: NCT05226117 .