275MO - Neoadjuvant sacituzumab govitecan, followed by radical cystectomy, for patients with muscle-invasive bladder cancer (MIBC): Updated interim results of SURE-01 trial

Background

Sacituzumab Govitecan (SG) is an antibody-drug conjugate composed of an anti-Trop-2 antibody plus SN-38 (a topoisomerase-I inhibitor) with FDA approval for advanced urothelial carcinoma. The open-label phase II SURE-01 study (NCT05226117) is evaluating neoadjuvant SG followed by radical cystectomy (RC) in patients (pts) with Muscle-Invasive Bladder Cancer (MIBC). We herein report results from an interim analysis.

Methods

Pts with cT2-4N0M0 MIBC with pure/predominant urothelial carcinoma histology, who were ineligible for or refused cisplatin-based chemotherapy, received 4 cycles of SG 10 mg/kg (days 1,8 q3w) followed by RC. Pts with clinical complete response (cCR, defined as negative MRI, cystoscopy, and ctDNA assays) who refused RC were offered to redo transurethral resection of bladder tumor (re-TURBT). Post-surgical management followed standard practice. The primary endpoint was the proportion of ypT0N0. Treatment-related adverse events (TRAEs) and safety were assessed with CTCAE v.5.0 criteria. UGT1A1 polymorphism, tumor samples genomic profiling, ctDNA analysis (Signatera assay) constituted the biomarker analyses.

Results

From 03/22 to 12/23, 25 pts (median age: 71y) were enrolled. 28.0% had a cT3-4N0, 56% had a mixed/variant histology. After the initial 8 pts receiving SG 10 mg/kg, the study was amended with SG at 7.5 mg/Kg due to 2 Grade 5 (G5) AEs. Overall, the most common any-grade TRAEs were anemia (57%), diarrhea (36%), fatigue (20%). >G3 TRAEs occurred in 9 pts (36%), most frequently neutropenia and diarrhea (16% each). They were more common with homo/heterozygous UGT1A1*28 polymorphisms (62.5%) than wild-type (20%). 11 pts (44%) achieved a cCR, 4 did not receive surgery due to TRAEs (N=2) or disease progression (PD, N=2). 21 pts underwent RC (N=13) or re-TURBT (N=8). ypT0N0-x response was achieved in 11 pts (44%, 95%CI: 24.4-65.1), with 48% ypT£1N0-x. After a median follow-up of 22.3 months, 2 pts developed a PD; 6-month EFS was 80%.

Conclusions

The observed ypT0N0-x responses after neoadjuvant SG demonstrate promising activity in MIBC, unveiling a potential to avoid RC. Reduced dose of SG was feasible, and the data support the ongoing SURE-01 study in MIBC.

Clinical trial identification

NCT05226117.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Gilead Sciences, Inc; Merck Inc.

Disclosure

All authors have declared no conflicts of interest.