Initial Results From TROPHY-U-01: A Phase 2 Open-Label Study of Sacituzumab Govitecan in Patients with Metastatic Urothelial Cancer (mUC) After Failure of Platinum-Based Regimens or Immunotherapy

Immunomedics, Inc
Study Design: 
TROPHY-U-01. SG 10 mg/kg was given on days 1 and 8 every 21 days. Data on Cohort A in 35 of 100 pts with mUC who progressed after prior platinum-based and checkpoint inhibition was presented.
Pts who progress after platinum-based therapy or who don’t respond or don’t tolerate immunotherapy have limited treatment options and poor outcomes. Unfortunately, checkpoint inhibitors are ineffective for a majority of pts. Additional treatment options are needed. Sacituzumab Govitecan (SG) is a Trop-2-Directed Antibody-Drug Conjugate (ADC). Trop-2 is an epithelial cell surface antigen highly expressed in UC and a wide range of epithelial cancers. SG is distinct from other ADCs, with a high drug-to-antibody ratio. Linker hydrolysis releases the cytotoxic SN-38 in tumor tissue (intracellularly and in the tumor microenvironment. The payload for SG is SN-38, a Topo1 inhibitor and more potent active metabolite of irinotecan.
The primary objective was overall response rate (ORR). Secondary objectives included. safety/tolerability, duration of response (DOR), progression-free survival (PFS) and overall survival (OS).
Antibody-Drug Conjugates are increasing of interest in the treatment of mUC. These data demonstrate that SG has the potential to change the treatment landscape of mUC.
35 pts included in the interim analysis received ≥1 cycle of study treatment and had ≥1 on-treatment response assessment. The ORR was 29% (2 CR, 6 PR, 2 additional PRs pending confirmation). ORR was 25.0% in pts with liver metastases. 74% of pts demonstrated a reduction in tumor size at a median follow-up of 4.1 mos. 57% of pts are continuing treatment. SG was well tolerated, with a manageable, predictable, and consistent safety profile, with neutropenia and leukopenia as the main toxicities. Diarrhea and fatigue were observed.