Dr Tolaney on the FDA Approval of First-Line Sacituzumab Govitecan Plus Pembrolizumab for TNBC

“The data we’ve seen with the combination are a significant improvement and a clinically meaningful one, and so will be important for patients to have access to newer treatments.”

Sara M. Tolaney, MD, MPH, chief of the Division of Breast Oncology and associate director of the Susan F. Smith Center for Women’s Cancers and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed the significance of the FDA approval of first-line sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab (Keytruda) for patients with triple-negative breast cancer (TNBC).

On June 24, 2026, the FDA approved sacituzumab govitecan in combination with pembrolizumab (Keytruda) or pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex) for the first-line treatment of adult patients with unresectable locally advanced or metastatic TNBC whose tumors express PD-L1 (combined positive score [CPS] ≥ 10) as determined by an FDA-authorized test. The regulatory agency simultaneously approved sacituzumab govitecan as monotherapy for the first-line treatment of adult patients with unresectable locally advanced or metastatic TNBC who are not eligible to receive PD-1 or PD-L1 inhibitor–based therapy. These regulatory decisions were based on data from the phase 3 ASCENT-04/KEYNOTE-D19 (NCT05382286) and ASCENT-03 (NCT05382299) trials, respectively.

Tolaney highlighted that TNBC remains the most challenging to treat, with patients historically facing limited overall survival. Consequently, she emphasized that the development of newer therapeutic advancements is a critical priority for this patient population.

Tolaney then detailed the parameters of the ASCENT-04 trial, which enrolled patients who had not received prior treatment in the metastatic setting. The study population included patients with either de novo or recurrent TNBC, provided they were at least 6 months removed from the completion of adjuvant systemic therapy. A key requirement for enrollment was the central confirmation of PD-L1 expression, defined by a CPS of 10 or greater.

The trial was designed to compare the efficacy of sacituzumab govitecan combined with pembrolizumab vs a control arm comprising pembrolizumab plus physician’s choice of chemotherapy. The primary end point for this study was progression-free survival (PFS).

The data revealed that the combination resulted in a statistically significant and clinically meaningful improvement in PFS. Patients receiving the combination achieved a median PFS of 11.2 months (95% CI, 9.3-16.7) compared with 7.8 months (95% CI, 7.3-9.3) for those in the chemotherapy/pembrolizumab control group (HR, 0.65; 95% CI, 0.51-0.84; P = .0009).