Sacituzumab govitecan (TROP2-directed ADC delivering SN-38) extends PFS2 to 18.2mo vs chemo in 1L PD-(L)1–ineligible mTNBC

Sacituzumab govitecan (SG) is a TROP2-targeted antibody–drug conjugate that delivers the topoisomerase I inhibitor payload SN-38; in the Phase 3 ASCENT-03 trial (NCT05382299), previously untreated metastatic TNBC patients not eligible for PD-(L)1 inhibitors were randomized 1:1 to SG vs physician’s-choice chemo (paclitaxel, nab-paclitaxel, or gemcitabine/carboplatin) (N=558). With median OS follow-up 13.2 months, median PFS2 (time to progression on next-line therapy or death) was 18.2 vs 14.0 months (HR 0.70; p=0.0051) despite extensive crossover—82% of chemo-arm patients who received subsequent therapy got SG; 12-month PFS2 was 71% vs 59%. Benchmarks for 1L chemo in unselected mTNBC typically land around ~6–8 months median PFS (e.g., gemcitabine/carboplatin ~6.0mo; nab-paclitaxel/carboplatin ~8.3mo), so the earlier ASCENT-03 primary PFS gain (9.7 vs 6.9 months) and the downstream PFS2 separation suggest sequencing benefit rather than just “borrowing” SG’s effect via crossover.