Sacituzumab Govitecan Combo Reduces Progression, Death By 35% in Metastatic TNBC

Full results from the phase 3 ASCENT-04/KEYNOTE-D19 trial (NCT05382286) showed that sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) significantly improved progression-free survival (PFS) compared with standard chemotherapy plus pembrolizumab in patients with previously untreated, PD-L1-positive, locally advanced unresectable or metastatic triple-negative breast cancer (TNBC), with the data being published in The New England Journal of Medicine.^1,2

Topline Data from ASCENT-04

The median PFS, the trial's primary end point, was 11.2 months (95% CI, 9.3-16.7) in patients receiving sacituzumab govitecan plus pembrolizumab compared with 7.8 months (95% CI, 7.3-9.3) in those receiving chemotherapy plus pembrolizumab. This represented a 35% reduction in the risk of disease progression or death (HR, 0.65; 95% CI, 0.51-0.84; P <.001). Investigator-assessed PFS yielded similar results, with a median of 11.3 months (95% CI, 9.2-14.6) in the sacituzumab govitecan group and 8.3 months (95% CI, 7.3-9.3) in the chemotherapy group (HR, 0.67; 95% CI, 0.52-0.87).

The objective response rate (ORR) was 60% (95% CI, 53%-66%) for the sacituzumab govitecan plus pembrolizumab group and 53% (95% CI, 46%-60%) for the chemotherapy plus pembrolizumab group. Complete responses occurred in 13% and 8% of patients, respectively. Among patients who responded to treatment, the median duration of response was 16.5 months (95% CI, 12.7-19.5) with sacituzumab govitecan plus pembrolizumab vs 9.2 months (95% CI, 7.6-11.3) with chemotherapy plus pembrolizumab. At the time of this primary analysis, data for overall survival (OS) were immature, as 26% of patients had died, and the median was not reached in either group.

“Patients with PD-L1–positive metastatic [TNBC] continue to [have] limited options in the first-line setting,” Sara Tolaney, MD, MPH, chief of the division of Breast Oncology at Dana-Farber Cancer Institute and principal investigator of the ASCENT-04 study, said in a press release on the findings.¹ “As such, these very promising data with the novel combination of sacituzumab govitecan and pembrolizumab in frontline metastatic TNBC represent a meaningful step forward in establishing a potential new standard of care for this challenging disease.”

How Was the ASCENT-04 Trial Structured?

In this open-label, randomized trial, 443 patients were randomly assigned 1:1 to receive either sacituzumab govitecan (n = 221; 10 mg/kg on days 1 and 8 of 21-day cycles) plus pembrolizumab (200 mg on day 1) or physician’s choice of chemotherapy plus pembrolizumab (n = 222). Chemotherapy options included paclitaxel, nanoparticle albumin-bound paclitaxel (Abraxane), or gemcitabine plus carboplatin. Treatment continued until disease progression, unacceptable toxic effects, or death. Pembrolizumab was limited to a maximum of 35 cycles.

Patients were enrolled between October 17, 2022, and August 21, 2024. Baseline characteristics were balanced between the 2 groups. The median age was 54 years in the sacituzumab govitecan group and 55 years in the chemotherapy group. All patients had PD-L1–positive tumors, defined as a combined positive score (CPS) of 10 or higher. Additionally, 34% of patients in each group had metastatic disease at initial diagnosis, 18% had recurrent disease 6 to 12 months after curative-intent treatment, and 48% had recurrent disease more than 12 months after such treatment. Common metastatic sites included lymph nodes (72% and 69%), lungs (50% and 43%), and liver (25% and 26%), between each arm, respectively.

The primary end point was PFS as determined by blinded independent central review. Secondary end points included OS, ORR, duration of response, time to response, and safety.

Safety

Adverse events (AEs) of grade 3 or higher occurred in 71% of patients receiving sacituzumab govitecan plus pembrolizumab and 70% of those receiving chemotherapy plus pembrolizumab. However, the incidence of treatment discontinuation due to AEs was notably lower in the sacituzumab govitecan group (12%) than in the chemotherapy group (31%). AEs leading to death occurred in 3% of patients in each group.

The most common reasons for treatment discontinuation were disease progression (37% for sacituzumab govitecan and 55% for chemotherapy) and AEs (8% and 18%, respectively). For pembrolizumab, specifically, 9% of patients in the sacituzumab govitecan group and 13% in the chemotherapy group discontinued the drug due to AEs. Median follow-up at the time of data cutoff on March 3, 2025, was 14.0 months.

References

1. New England Journal of Medicine publishes phase 3 ASCENT-04/KEYNOTE-D19 results supporting Trodelvy^® plus Keytruda^® as a potential new standard of care in first-line PD-L1+ metastatic triple-negative breast cancer. News release. Gilead Sciences. January 21, 2026. Accessed January 22, 2026. https://tinyurl.com/47fy8jz9
2. Tolaney SM, de Azambuja E, Kalinsky K, et al. Sacituzumab govitecan plus pembrolizumab for advanced triple-negative breast cancer. N Engl J Med. 2026;394(4):354-366. doi:10.1056/NEJMoa2508959