Sacituzumab govitecan (TROP2 ADC) + pembrolizumab extends PFS vs chemo+pembro across TROP2, tBRCA, and HER2-low mTNBC subgroups

Sacituzumab govitecan (SG) is a TROP2-directed antibody–drug conjugate delivering SN-38, combined here with pembrolizumab (PD-1 inhibitor) as first-line therapy in the Phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286) in previously untreated PD-L1+ metastatic TNBC (n=443; randomized 1:1 vs gemcitabine/carboplatin or taxane chemotherapy + pembrolizumab). In preplanned exploratory biomarker analyses, SG+pembro improved BICR-assessed PFS vs chemo+pembro across TROP2 IHC H-score quartiles (Q1 HR 0.81; Q2 0.73; Q3 0.46; Q4 0.57), with median PFS rising from 8.4–9.2 months on chemo+pembro to 13.5–16.6 months in the higher TROP2 quartiles (Q3/Q4). Benefit was also seen in tBRCA WT (median PFS 9.6 vs 7.4 months; HR 0.67) while tBRCA-mut tumors (~20% of tested; n=71) showed an imprecise effect estimate (16.6 vs 12.9 months; HR 0.88), and PFS favored SG+pembro in both HER2 IHC 0 (16.6 vs 9.0 months; HR 0.69) and HER2-low (HR 0.67) subgroups; safety details for these subgroup cuts were not reported in this abstract (overall safety previously described as consistent with each agent).