Background
Phase III, open-label RCT. N=443 with previously untreated PD-L1 CPS≥10 unresectable locally advanced or metastatic TNBC. PD-L1 by 22C3 pharmDx (CPS≥10 required; ~45% of screened mTNBC). Stratified by region and prior (neo)adjuvant chemotherapy.
Interventions and follow up
Arm A: Sacituzumab govitecan (SG) 10mg/kg IV days 1 and 8 q3wk + pembrolizumab 200mg q3wk (N=221)
Arm B: Investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) + pembrolizumab 200mg q3wk (N=222)
Primary endpoint: PFS by BICR
mFollow up: NR at data cutoff
Arm B: Investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine-carboplatin) + pembrolizumab 200mg q3wk (N=222)
Primary endpoint: PFS by BICR
mFollow up: NR at data cutoff
Results
PFS: 11.2 vs 7.8mo, HR 0.65, 95% CI 0.51–0.84, P<.001
ORR: 60% vs 53%
Median DOR: 16.5 vs 9.2mo
OS: not yet mature
ORR: 60% vs 53%
Median DOR: 16.5 vs 9.2mo
OS: not yet mature
Adverse events
Overall (grade ≥3): similar between arms
Discontinuation due to AEs: 12% (SG+pembro) vs 31% (chemo+pembro)
SG arm: neutropenia, diarrhea, nausea
Taxane arm: peripheral neuropathy
Discontinuation due to AEs: 12% (SG+pembro) vs 31% (chemo+pembro)
SG arm: neutropenia, diarrhea, nausea
Taxane arm: peripheral neuropathy
Conclusions
SG + pembrolizumab significantly improved PFS vs chemotherapy + pembrolizumab in PD-L1 CPS≥10 mTNBC (HR 0.65), with substantially lower discontinuation (12% vs 31%) — a more tolerable and active regimen. Directly challenges KEYNOTE-355 as 1L standard in this biomarker-selected population.
Key Limitations
Restricted to CPS≥10 (~45% of mTNBC), limiting generalizability. OS immature; 3.4-month absolute PFS gain may not reflect long-term benefit. Comparator pooled 3 regimens (heterogeneity). Open-label. No pre-planned crossover; salvage patterns may confound OS.
Clinical Context
Directly challenges KEYNOTE-355 (pembrolizumab + chemo) as 1L standard in CPS≥10 mTNBC. Lower discontinuation (12% vs 31%) and longer DOR (16.5 vs 9.2mo) suggest clinical advantage. Concurrent ASCENT-03 (SG monotherapy 1L, unselected) provides context. FDA review anticipated. ESMO-MCBS pending OS data.