Sacituzumab Govitecan Plus Pembrolizumab Significantly Prolongs PFS in PD-L1-Positive Triple-Negative Breast Cancer

Key Clinical Takeaways: 

• Design/Population: In this phase 3, open-label trial, 443 patients with previously untreated, PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer were randomzied to receive sacituzumab govitecan plus pembrolizumab or pembrolizumab plus chemotherapy. 
• Key Outcomes: Sacituzumab govitecan combined with pembrolizumab significantly improved median progression-free survival compared with pembrolizumab plus chemotherapy (11.2 vs 7.8 months). Objective response rates were higher with sacituzumab govitecan (60% vs 53%), with longer median duration of response, while overall survival data were immature at the time of analysis.
• Clinical Relevance: These findings suggest that incorporating a Trop-2–directed antibody–drug conjugate into first-line immunotherapy-based treatment may improve disease control in PD-L1–positive advanced triple-negative breast cancer, supporting further evaluation of this combination in clinical practice.

According to results from the phase 3 ASCENT-04 trial, sacituzumab govitecan plus pembrolizumab significantly prolonged progression-free survival (PFS) compared to pembrolizumab plus chemotherapy among previously untreated patients with PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer (TNBC). 

“[TNBC] is an aggressive breast cancer subtype, and there remains an unmet need to improve outcomes in patients with previously untreated, PD-L1–positive, locally advanced unresectable or metastatic triple-negative breast cancer,” stated Sara Tolaney, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, and coauthors. 

In this open-label study, 443 patients were randomized 1:1 to receive pembrolizumab plus sacituzumab govitecan (n = 221) or pembrolizumab plus physician’s choice chemotherapy (n = 222). The primary end point was PFS, assessed via blinded independent central review. Key secondary end points included overall survival (OS), objective response rate (ORR), duration of response, and safety.

At analysis, median PFS was 11.2 months in the sacituzumab govitecan plus pembrolizumab arm and 7.8 months in the pembrolizumab plus chemotherapy arm (hazard ratio [HR], 0.65; 95% CI, 0.51 to 0.84; P <.001). Median ORR was 60% in the sacituzumab govitecan plus pembrolizumab arm and 53% in the pembrolizumab plus chemotherapy arm, with median durations of response of 16.5 months and 9.2 months, respectively. OS data were immature at analysis. 

Grade ≥3 adverse events were reported in 71% of patients in the sacituzumab govitecan plus pembrolizumab arm and 70% of patients in the pembrolizumab plus chemotherapy arm. Adverse events led to treatment discontinuations in 12% and 31% of patients, respectively. Adverse events led to death in 3% of patients in each treatment arm. 

“Sacituzumab govitecan plus pembrolizumab led to significantly longer [PFS] than chemotherapy plus pembrolizumab among patients with previously untreated, PD-L1–positive, advanced triple-negative breast cancer,” concluded Dr Tolaney et al. 

Source: 

Tolaney SM, De Evandro A, Kalinsky K, et al. Sacituzumab govitecan plus pembrolizumab for advanced triple-negative breast cancer. N Engl J Med. Published online: January 21, 2026. doi:10.1056/NEJMoa2508959