Breast Cancer / Videos & Podcasts 07/13/2026

ASCENT-03 and ASCENT-04 Lead to New Indications for Sacituzumab Govitecan in TNBC

Professional headshot of a confident woman with dark hair and a friendly expression, suitable for OncUpdates and healthcare-related content. Sara Tolaney, MD, MPH Smiling man with beard wearing a white shirt, professional headshot, suitable for oncology or cancer research content, emphasizing healthcare and medical expertise. Rahul Gosain, MD, MBA Oncologist smiling in white coat, highlighting cancer research and treatment expertise, with a bow tie, in a bright medical setting. Rohit Gosain, MD
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Key Points

  • The FDA approved front-line sacituzumab govitecan with or without pembrolizumab, depending on PD-L1 status, for metastatic triple-negative breast cancer (TNBC) based on the ASCENT-03 and ASCENT-04 trials.
  • Sacituzumab govitecan–based treatment improved subsequent survival outcomes versus chemotherapy-based treatment despite significant crossover to sacituzumab govitecan in each trial.

New Approvals for Sacituzumab Govitecan Based on ASCENT-03 and ASCENT-04

Oncology Brothers podcast cohosts Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, met with Sara Tolaney, MD, MPH, of Dana-Farber Cancer Institute, to discuss the June 24, 2026, FDA approval of sacituzumab govitecan for two indications in patients with TNBC. 

The first indication, based on ASCENT-03, was for first-line single-agent sacituzumab govitecan in patients with unresectable locally advanced or metastatic TNBC who were not candidates for PD-1 or PD-L1 inhibitors. The second indication, based on ASCENT-04, was for first-line sacituzumab govitecan plus pembrolizumab in patients with PD-L1–positive unresectable locally advanced or metastatic TNBC.

ASCENT-03: Sacituzumab Govitecan Monotherapy for Metastatic TNBC

The ASCENT-03 trial enrolled 558 patients with previously untreated, advanced TNBC who were not eligible for PD-1 or PD-L1 inhibitors. Overall, the median progression-free survival (PFS) was 9.7 months (95% CI, 8.1-11.1) with sacituzumab govitecan and 6.9 months (95% CI, 5.6-8.2) with chemotherapy (HR, 0.62; 95% CI, 0.5-0.77; P < .001). The objective response rates were 48% (95% CI, 42-54) with sacituzumab govitecan and 46% (95% CI, 40-52) with chemotherapy. median response duration was 12.2 months (95% CI, 9.7-13.8) and 7.2 months (95% CI, 5.7-8.4), respectively.

Grade 3 or higher adverse events (AEs) occurred in 66% of the sacituzumab govitecan group and 62% of the chemotherapy group. The most frequent AEs were neutropenia (43%), diarrhea (9%), and leukopenia (7%) for sacituzumab govitecan and neutropenia (41%), anemia (16%), and leukopenia (13%) for chemotherapy. Only 4% of patients discontinued sacituzumab govitecan due to AEs, while 12% discontinued 1 or more chemotherapy drugs due to AEs.

ASCENT-04: Sacituzumab Govitecan Plus Pembrolizumab for PD-L1–Positive Metastatic TNBC

The ASCENT-04 trial enrolled 443 patients with previously untreated, PD-L1–positive, locally advanced unresectable or metastatic TNBC. The median PFS was 11.2 months (95% CI, 9.3-16.7) with sacituzumab govitecan plus pembrolizumab and 7.8 months (95% CI, 7.3-9.3) with chemotherapy plus pembrolizumab (HR, 0.65; 95% CI, 0.51-0.84; P < .001). The objective response rates were 60% (95% CI, 53-66) and 53% (95% CI, 46-60), and median duration of response among responders was 16.5 months (95% CI, 12.7-19.5) and 9.2 months (95% CI, 7.6-11.3) for the sacituzumab govitecan and chemotherapy groups, respectively. Overall survival data were immature. 

Grade 3 or higher AEs occurred in 71% of the sacituzumab plus pembrolizumab group and 60% of the chemotherapy plus pembrolizumab group, and 12% and 31% of patients discontinued treatment due to AEs, respectively. In addition, 3% of patients in each group died due to AEs. 

ASCO 2026 Data Updates

Researchers presented updated data for ASCENT-03 and ASCENT-04 at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO 2026). The analyses covered subsequent therapies and PFS after subsequent treatment (PFS2) in patients who discontinued first-line sacituzumab govitecan or chemotherapy-based first-line treatment in either trial.

In ASCENT-03, 27% of the sacituzumab govitecan group and 14% of the chemotherapy group remained on treatment. The most common subsequent therapies after sacituzumab govitecan were platinum-based chemotherapy, taxanes, and gemcitabine. Following chemotherapy, the most common subsequent therapies were sacituzumab govitecan, capecitabine, platinum-based chemotherapy, and trastuzumab deruxtecan. The median PFS2 was 18.2 months (95% CI, 15.9–not reached [NR]) in the sacituzumab govitecan group versus 14 months (95% CI, 12.5-17.4) in the chemotherapy group (HR, 0.70; 95% CI, 0.55-0.90).

In ASCENT-04, 43% of the sacituzumab govitecan group and 23% of the chemotherapy group remained on treatment. The most common subsequent therapies after sacituzumab govitecan plus pembrolizumab were taxanes, platinum-based chemotherapy, and capecitabine. Following chemotherapy plus pembrolizumab, the most common subsequent therapies were sacituzumab govitecan, taxanes, and capecitabine. The median PFS2 was not reached (95% CI, NR-NR) in the sacituzumab govitecan group versus 21 months (95% CI, 16-NR) in the chemotherapy group (HR, 0.67; 95% CI, 0.48-0.95).

The ASCENT-04 trial data support sacituzumab govitecan plus pembrolizumab as frontline standard of care for PD-L1–positive patients with metastatic TNBC, while the ASCENT-03 findings establish sacituzumab govitecan alongside datopotamab deruxtecan as standard frontline options for PD-L1–negative patients with metastatic TNBC, Dr. Rohit Gosain said.