Clinicaltrials.gov identifier:
Sponsor:
Immunomedics, Inc
Enrollment:
100
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.
Rationale:
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.
Endpoints:
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).
Comments:
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.
Results:
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.
