130 Sacituzumab Govitecan (SG) + Pembrolizumab (Pembro) Vs Chemotherapy (Chemo) + Pembro in Previously Untreated PD-L1–Positive Advanced Triple-Negative Breast Cancer (TNBC): Primary Results From the Randomized Phase 3 ASCENT-04/KEYNOTE-D19 Study

Background

Although PD-1/PD-L1 inhibitors plus chemotherapy have expanded treatment options for previously untreated PD-L1–positive advanced triple-negative breast cancer (TNBC), there still remains a critical unmet need to improve outcomes. Sacituzumab govitecan previously demonstrated significant clinical benefit in pretreated metastatic TNBC. We report results from the ASCENT-04/KEYNOTE-D19 studyin patients with previously untreated, PD-L1–positive (combined positive score ≥ 10; 22C3 assay) locally advanced unresectable or mTNBC.

Methods

Patients were randomly assigned 1:1 to sacituzumab govitecan (10 mg/kg IV, day 1 and 8) plus pembrolizumab (200 mg, day 1, max 35 cycles) in 21-day cycles or chemotherapy (gemcitabine plus carboplatin, paclitaxel, nab-paclitaxel) plus pembrolizumab until disease progression or unacceptable toxicity. Randomization was stratified by curative treatment-free interval, geography, and prior exposure to anti–PD-L1 therapy in the curative setting. Primary end point was progression-free survival (PFS) by blinded independent central review (BICR). Key secondary end points include overall survival (OS); objective response rate (ORR) and duration of response (DOR) by BICR; and safety.

Results

A total of443 patients were randomized at a 1:1 ratio: 221 to sacituzumab govitecan plus pembrolizumab and 222 to chemotherapy plus pembrolizumab. The median follow-up was 14 months. Sacituzumab govitecan plus pembrolizumab showed a significant improvement in PFS by BICR compared with chemotherapy plus pembrolizumab (HR, 0.65; 95% CI, 0.51-0.84; P = .0009; Table). Median DOR was 16.5 months for sacituzumab govitecan plus pembrolizumab vs 9.2 months for chemotherapy plus pembrolizumab (Table). Although OS data were immature, a positive early trend in OS improvement was also noted. The most frequent (≥ 10% of patients) grade 3 or higher treatment-emergent adverse events (TEAEs) with sacituzumab govitecan plus pembrolizumab were neutropenia (43%) and diarrhea (10%); and with chemotherapy plus pembrolizumab were neutropenia (45%), anemia (16%), and thrombocytopenia (14%).

Conclusions

Sacituzumab govitecan plus pembrolizumab led to a statistically significant and clinically meaningful improvement in PFS vs chemotherapy plus pembrolizumab with durable responses, no new safety concerns for sacituzumab govitecan or pembrolizumab, and a lower rate of treatment discontinuation due to TEAEs in patients with previously untreated, PD-L1–positive advanced TNBC. These data support the use of sacituzumab govitecan plus pembrolizumab as a potential new standard of care treatment in this patient population.