Alpelisib + Sacituzumab Govitecan Yields 36% ORR (50% in TNBC) at Recommended Phase-2 Dose

In a 3 + 3 phase I dose-escalation study (NCT05143229), 12 women with heavily pre-treated, HER2-negative metastatic breast cancer received daily alpelisib (an α-specific PI3K inhibitor) plus sacituzumab govitecan (A TROP-2 ADC) on days 1 & 8 every 21 days. Among 11 evaluable patients (7 triple-negative, 5 HR⁺; 25% had prior ADCs), investigator-assessed ORR was 36% overall—50% in TNBC and 20% in HR-positive disease—while the clinical-benefit rate (CR + PR + SD > 24 wk) reached 64%. Median PFS was 5.7 months; three of four responders maintained benefit > 6 months (median DoR 14.9 mo). Grade ≥3 toxicities matched the agents’ monotherapy profiles: neutropenia (33%), diarrhea (17%), electrolyte disturbances (34%), and hyperglycemia (16%); one DLT (grade 3 hyperbilirubinemia) occurred at alpelisib 250 mg + SG 10 mg kg⁻¹. No grade 5 events arose.