The ASCENT-04/KEYNOTE-D19 trial evaluated sacituzumab govitecan, a TROP-2–directed antibody–drug conjugate, in combination with pembrolizumab, an anti–programmed cell death protein 1 monoclonal antibody, as first-line therapy for programmed death-ligand 1 (PD-L1)-positive (defined as a combined positive score ≥10), advanced triple-negative breast cancer (TNBC). A total of 443 patients with locally advanced, unresectable, or metastatic TNBC were randomized 1:1 to receive sacituzumab govitecan in combination with pembrolizumab or chemotherapy (gemcitabine + carboplatin, paclitaxel, nab-paclitaxel) in combination with pembrolizumab. The primary endpoint was progression-free survival (PFS) assessed by blinded independent central review (BICR), with key secondary endpoints including overall survival (OS), objective response rate (ORR), duration of response (DOR) by BICR, safety, and quality of life.
After randomization, 221 patients received sacituzumab govitecan in combination with pembrolizumab and 222 patients received chemotherapy in combination with pembrolizumab. Baseline characteristics were balanced between the two groups. With a median follow-up of 14 months, the sacituzumab govitecan arm (median PFS: 11.2; 95% confidence interval [CI], 9.3-16.7 months) demonstrated a statistically significant improvement in PFS by BICR compared with the chemotherapy arm (median PFS, 7.8; 95% CI, 7.3-9.3 months), (hazard ratio, 0.65; 95% CI, 0.51-0.84; P<.001). ORR (60% vs 53%) and median DOR (16.5 vs 9.2 months) also favored the sacituzumab govitecan arm compared with the chemotherapy arm. Although OS data remain immature, early trends suggested a potential survival benefit for the sacituzumab govitecan arm. Common grade ≥3 treatment-emergent adverse events included neutropenia (43%) and diarrhea (10%) for the sacituzumab govitecan arm and neutropenia (45%), anemia (16%), and thrombocytopenia (14%) for the chemotherapy arm.
These results highlight the clinical efficacy and tolerability of sacituzumab govitecan in combination with pembrolizumab, offering a significant improvement in PFS and durable responses with manageable toxicity. The findings support sacituzumab govitecan in combination with pembrolizumab as a potential new first-line standard-of-care treatment option for patients with advanced TNBC.
Source: Tolaney S, et al. 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. Presented at: 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract LBA109.