sacituzumab govitecan

Overview

Sacituzumab govitecan is an antibody-drug conjugate (ADC) that combines a humanized anti-TROP-2 (encoded by TACSTD2) monoclonal antibody with SN-38, the active metabolite of irinotecan (a topoisomerase I inhibitor), via a hydrolyzable linker. TROP-2 is broadly overexpressed in epithelial tumors including urothelial carcinoma, making it an attractive target for ADC-based bladder-preservation strategies. The drug is being evaluated in combination with radiotherapy (RT) on the rationale that SN-38-mediated DNA damage may synergize with RT-induced double-strand breaks, and that TROP-2 targeting localizes cytotoxic payload delivery to the tumor.

Evidence in the corpus

The ROBIN GenRad center (Cleveland Clinic / Emory) is running the RAD-SG trial (NCT05833867, Phase I/II) evaluating RT + sacituzumab govitecan for definitive bladder-preservation treatment in muscle-invasive bladder cancer (MIBC). Preliminary results at the time of this white paper report that the combination was safe and feasible, with only grade-1 toxicities observed. Accrual and formal efficacy evaluation were ongoing. PMID:41941260
The paper contextualizes sacituzumab govitecan as part of a broader GenRad portfolio combining RT with novel systemic agents in BLCA and HNSC, with longitudinal biospecimen collection and multi-omics (spatial transcriptomics, scRNA-seq) planned to characterize the tumor microenvironment response to RT + ADC. PMID:41941260

Resistance mechanisms

No resistance mechanisms reported in the corpus at this time.

Cancer types (linked)

BLCA — muscle-invasive bladder cancer; primary disease site in the RAD-SG trial.

Sources

PMID:41941260 — Gregucci et al. 2026, Clin Cancer Res. ROBIN white paper; GenRad RAD-SG (NCT05833867) preliminary safety data.

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