Breast Cancer VJToday

FDA approves sacituzumab govitecan as monotherapy and with pembrolizumab in first-line triple-negative breast cancer

On June 24, 2026, the U.S. Food and Drug Administration (FDA) approved sacituzumab govitecan, a TROP-2-directed antibody-drug conjugate (ADC), as both a first-line monotherapy for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who are ineligible for PD-(L) inhibitor-based treatment and in combination with pembrolizumab for patients with PD-L1-positive disease.1 While immunotherapy has improved outcomes for patients with PD-L1-positive TNBC, treatment options for those ineligible for PD-1/PD-L1 inhibitors have remained limited, relying largely on chemotherapy. Even in PD-L1-positive disease, there remains a need for more effective first-line regimens capable of extending disease control beyond what has been achieved with current standards of care.2

Approval of sacituzumab govitecan monotherapy and in combination with pembrolizumab was supported by results from the Phase III ASCENT-03 (NCT05382299) and ASCENT-04/KEYNOTE-D19 (NCT05382286) trials respectively. In ASCENT-03, which enrolled 558 patients who were not candidates for immunotherapy, the primary endpoint of progression-free survival (PFS) was met, where median PFS was 9.7 months (95% CI: 8.1, 11.1) versus 6.9 months (95% CI: 5.6, 8.2) in the sacituzumab govitecan and chemotherapy arms respectively. Confirmed objective response rates (ORR) were 50% (95% CI: 44, 56) and 47% (95% CI, 40 to 52) in the respective arms.3

The ASCENT-04/KEYNOTE-D19 trial assessed pembrolizumab with SG or chemotherapy in 443 patients in a 1:1 fashion. Addition of sacituzumab govitecan resulted in the primary endpoint, PFS, being achieved. Median PFS reached 11.2 months compared with 7.8 months for chemotherapy plus pembrolizumab, translating to a 35% reduction in the risk of progression or death (HR, 0.65: 95% CI, 0.51, 0.84). Confirmed ORR were 61% (95% CI: 55, 68) and 55% (95% CI: 48, 62), respectively.4

Jason Mouabbi, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, provides his commentary on the ASCENT-04 trial, saying:

“The next frontier in the world of oncology and similarly for the third subtype of breast cancer, the triple negatives, we have the ASCENT-04 study, another antibody drug conjugate targeting TROP-2 that can be combined with immunotherapy pembrolizumab. [The trial] is going to define this field going forward and can be part of the first-line therapy for triple negative that are immunogenic with a positive PD-L1.”

These approvals establish sacituzumab govitecan as a new first-line treatment option across PD-L1 subgroups, expanding the role of antibody-drug conjugates earlier in the management of metastatic TNBC.

References:

  1. Center for Drug Evaluation and Research. FDA approves sacituzumab govitecan-hziy as monotherapy and in combination with pembrolizumab for first-line treatment of triple-negative breast cancer [Internet]. U.S. Food and Drug Administration. 2026 [cited 2026 Jun 24]. Available from: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-monotherapy-and-combination-pembrolizumab-first-line
  2. Hennessy MA, Terman E, Idossa D, LeVee A, Leon-Ferre RA, McArthur H, et al. Advanced triple-negative breast cancer: Emerging therapies and a changing treatment landscape. American Society of Clinical Oncology Educational Book. 2026 Jun;46(3). doi:10.1200/edbk-26-520506
  3. Cortés J, Punie K, Barrios C, Hurvitz SA, Schneeweiss A, Sohn J, et al. Sacituzumab Govitecan in untreated, advanced triple-negative breast cancer. New England Journal of Medicine. 2025 Nov 13;393(19):1912–25. doi:10.1056/nejmoa2511734
  4. Tolaney SM, de Azambuja E, Kalinsky K, Loi S, Kim S-B, Yam C, et al. Sacituzumab Govitecan plus pembrolizumab for advanced triple-negative breast cancer. New England Journal of Medicine. 2026 Jan 22;394(4):354–66. doi:10.1056/nejmoa2508959