FDA approves first-line Trodelvy options with or without Keytruda for metastatic TNBC

FDA has approved two first-line Trodelvy-based treatment options for adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC): Trodelvy (sacituzumab govitecan-hziy) alone for patients who are not candidates for PD-1/PD-L1 inhibitor–based therapy, and Trodelvy plus Keytruda (pembrolizumab) or Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) for patients with PD-L1–positive disease.

The approvals move Trodelvy earlier in the treatment course for metastatic TNBC, an aggressive breast cancer subtype with limited treatment options. This matters because first-line treatment choice can be pivotal, and many patients with metastatic TNBC may not go on to receive later-line therapy.

Trodelvy is a Trop-2–directed antibody-drug conjugate that delivers SN-38, a topoisomerase I inhibitor, to cancer cells. Keytruda is a programmed death receptor-1 (PD-1) inhibitor that helps restore antitumor immune activity. The combination is for patients whose tumors express PD-L1 with a combined positive score of at least 10 by an FDA-authorized test.

The Trodelvy monotherapy option was approved based on the results from ASCENT-03, an open-label randomized trial of 558 patients who had not received prior systemic therapy for advanced disease and were not candidates for PD-1 or PD-L1 inhibitor therapy. Patients received Trodelvy or physician’s choice of chemotherapy.

Median progression-free survival was 9.7 months with Trodelvy versus 6.9 months with chemotherapy, corresponding to a 38% lower risk of disease progression or death. Confirmed objective response rates were 50% and 47%, respectively. Median duration of response was 12.2 months with Trodelvy versus 7.2 months with chemotherapy. Follow-up was not yet long enough to determine whether overall survival also improved.

The Trodelvy-Keytruda combination approval was based on ASCENT-04/KEYNOTE-D19, a single open-label randomized trial of 443 patients with PD-L1–positive locally advanced or metastatic TNBC. Patients received Trodelvy plus Keytruda or physician’s choice of chemotherapy plus Keytruda.

Median progression-free survival was 11.2 months with Trodelvy plus Keytruda compared with 7.8 months with chemotherapy plus Keytruda, corresponding to a 35% lower risk of disease progression or death. Confirmed objective response rates were 61% and 55%, respectively, with complete responses in 12% and 8% of patients. Median duration of response was 16.5 months with Trodelvy plus Keytruda compared with 9.2 months with chemotherapy plus Keytruda. Whether the regimen improves overall survival will require longer follow-up.

Safety considerations include the known toxicities of Trodelvy and pembrolizumab. Trodelvy carries a boxed warning for severe neutropenia and diarrhea, while Keytruda and Keytruda Qlex labeling includes warnings for severe and fatal immune-mediated adverse reactions. In the combination trial, common adverse reactions included cytopenias, diarrhea, nausea, fatigue, alopecia, and rash.

Gilead said the National Comprehensive Cancer Network (NCCN) now recommends Trodelvy with or without pembrolizumab as a category 1 preferred first-line treatment option for metastatic TNBC.

“For people living with metastatic TNBC, the first treatment choice can be pivotal, as many patients may not have the opportunity to receive subsequent therapies,” said Sara Tolaney, MD, MPH, chief of the Division of Breast Oncology at Dana-Farber Cancer Institute and a principal investigator of ASCENT-03 and ASCENT-04. “This approval is heartening news for patients and the clinical community, and I believe offers a practice-changing first-line treatment option for all patients across PD-L1 status.”

Sources: Gilead Sciences. 2026 June 24. [Press release]. US FDA approves Trodelvy for first-line treatment of metastatic triple-negative breast cancer; Merck. 2026 June 25. [Press release]. FDA approves Keytruda and Keytruda Qlex, each with Trodelvy as first-line treatment of PD-L1+ advanced triple-negative breast cancer; Food and Drug Administration. 2026 June 24. [News release]. FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer