TROPHY-u-01: A Phase II Open-Label Study of Sacituzumab Govitecan (IMMU-132) in Patients with Advanced Urothelial Cancer after Progression on Platinum-Based Chemotherapy And/or Anti-Pd-1/pd-l1 Checkpoint Inhibitor Therapy.

TPS3153 Background: Patients (pts) with advanced urothelial cancer (UC) who progress after checkpoint inhibitor (CPI) therapy (following failure of or ineligibility for platinum-based chemotherapy) have limited options. Trop-2 is an epithelial cell surface antigen overexpressed in UC (Avellini. Oncotarget 2017). Sacituzumab govitecan (SG) is an antibody-drug conjugate that targets Trop-2 and delivers the active metabolite SN38 of the topoisomerase I inhibitor irinotecan to tumor cells (Starodub. Clin Cancer Res 2015). In a phase 1/2 trial, pts with advanced cancers received SG on days 1 and 8 of a 21-day cycle. In the UC cohort, 45 evaluable pts received SG 10 mg/kg with a median of 2 (range 1–6) prior therapies. Objective response rate (ORR) was 31%; median duration of response was 12.9 mo. Grade ≥3 adverse events in ≥5% of pts were neutropenia/neutrophil count decreased (38%), anemia (13%), hypophosphatemia (11%), diarrhea (9%), fatigue (9%), and febrile neutropenia (7%). Median progression-free survival (PFS) was 7.3 mo and overall survival (OS) 16.3 mo (Tagawa 2019 ASCO Genitourinary Cancers Symposium). These results warrant further investigation in a dedicated phase 2 trial. Methods: TROPHY-U-01 (NCT03547973) is a single-arm, global phase 2 trial evaluating the antitumor activity of SG (10 mg/kg on days 1 and 8 of a 21-day cycle) in 140 pts with advanced UC and measurable disease. Patients are also required to have an Eastern Cooperative Oncology Group Performance Status score of 0 or 1 and creatinine clearance ≥30 mL/min. The pivotal cohort (Cohort 1: progression after both platinum chemotherapy and CPI) will enroll 100 evaluable pts in a Simon 2-stage design with > 90% power accounting for dropouts to exclude the null hypothesis or ORR < 12%; an exploratory cohort (Cohort 2: 40 pts) includes platinum-ineligible pts who progress after prior CPI. The primary objective is ORR per RECIST 1.1, assessed by central review. Secondary objectives include response duration, PFS, and OS. Adverse events, pharmacokinetics, and tissue correlates will also be assessed. Enrollment began August 2018. Clinical trial information: NCT03547973.