Sacituzumab govitecan (TROP2 ADC delivering SN-38) extends PFS vs taxane or gem/carbo across Trop-2, tBRCA, and HER2-low subgroups in 1L advanced TNBC

Sacituzumab govitecan (SG) is a TROP2-targeted antibody–drug conjugate delivering the topo-I inhibitor payload SN-38; in the Phase 3 ASCENT-03 trial (NCT05382299), previously untreated locally advanced unresectable/metastatic TNBC patients not eligible for PD-(L)1 inhibitors were randomized 1:1 to SG vs physician’s-choice chemo (taxane or gemcitabine+carboplatin; n=588). In preplanned exploratory biomarker analyses, SG improved BICR PFS across Trop-2 IHC H-score quartiles (HR 0.54–0.84; e.g., Q1 mPFS 8.5 vs 5.5mo, HR 0.54; Q4 9.9 vs 8.1mo, HR 0.60), across tumor BRCA status (WT 8.8 vs 6.9mo, HR 0.70; mut 12.7 vs 8.3mo, HR 0.59), and across HER2 IHC 0 vs HER2-low (IHC0 8.3 vs 5.6mo, HR 0.63; HER2-low HR 0.74). The control-arm PFS here (≈5–8mo depending on subgroup/chemo) is broadly in the expected range for 1L chemo in advanced TNBC, while PD-L1–positive patients who can receive pembrolizumab+chemo in KEYNOTE-355 achieve mPFS ~9.7mo vs 5.6mo with chemo alone (CPS≥10)—a reminder that ASCENT-03 is aiming to “upgrade” outcomes specifically for the PD-(L)1-ineligible slice rather than replace IO where it’s indicated.