The European Commission (EC) has granted marketing authorization for Trodelvy (sacituzumab govitecan) in combination with Keytruda (pembrolizumab) for the first-line treatment of certain patients with triple-negative breast cancer (TNBC).
The combination is authorized for adults with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic disease and whose tumors express PD-L1 with a combined positive score (CPS) ≥10.
According to Gilead Sciences, Trodelvy plus Keytruda is the first and only antibody-drug conjugate (ADC) plus immunotherapy combination approved for first-line metastatic TNBC in the European Union’s 27 member states, as well as Norway, Iceland and Liechtenstein.
The authorization follows an earlier EC decision on June 23, 2026, approving Trodelvy as monotherapy for adults with unresectable locally advanced or metastatic TNBC who have not previously received systemic therapy for metastatic disease and are not candidates for PD-1 or PD-L1 inhibitor therapy. Together, the indications extend the use of Trodelvy-based first-line treatment to different populations according to eligibility for PD-1/PD-L1-directed therapy.
ASCENT-04/KEYNOTE-D19
The latest approval is based on results from the Phase III ASCENT-04/KEYNOTE-D19 trial (NCT05382286), an international, randomized, open-label study evaluating sacituzumab govitecan plus pembrolizumab against physician’s-choice chemotherapy plus pembrolizumab in previously untreated patients with PD-L1-positive locally advanced inoperable or metastatic TNBC.
A total of 443 patients were randomized: 221 to sacituzumab govitecan plus pembrolizumab and 222 to chemotherapy plus pembrolizumab.
Median progression-free survival was 11.2 months with sacituzumab govitecan plus pembrolizumab compared with 7.8 months with chemotherapy plus pembrolizumab.
The hazard ratio for disease progression or death was 0.65 (95% CI, 0.51–0.84; P<0.001), corresponding to a 35% reduction in the risk of disease progression or death.
The objective response rate was 60% with sacituzumab govitecan plus pembrolizumab and 53% with chemotherapy plus pembrolizumab. Among patients who responded, median duration of response was 16.5 months versus 9.2 months, respectively.
Overall survival data were immature at the time of the published analysis.
Grade 3 or higher adverse events occurred in 71% of patients receiving sacituzumab govitecan plus pembrolizumab and 70% of those receiving chemotherapy plus pembrolizumab. Adverse events led to treatment discontinuation in 12% and 31%, respectively, while adverse events leading to death occurred in 3% of patients in each group.
Evandro de Azambuja, MD, PhD, Head of the Medical Support Team at the Jules Bordet Institute and an investigator of ASCENT-04, described the authorization as an advance for patients with PD-L1-positive metastatic TNBC, noting that the regimen provides a new first-line treatment option for this population.
What Is Trodelvy?
Trodelvy (sacituzumab govitecan) is a Trop-2-directed antibody-drug conjugate. It uses an antibody targeting Trop-2 linked to SN-38, a topoisomerase I inhibitor payload. Trop-2 is highly expressed in several tumor types, including breast cancer.
Trodelvy is designed to deliver SN-38 to Trop-2-expressing tumor cells and can also affect surrounding cells through a bystander effect.
Beyond its newly expanded first-line role, Trodelvy is already used in later-line metastatic TNBC and in certain previously treated patients with HR-positive/HER2-negative metastatic breast cancer.
The decision follows the U.S. FDA approval on June 24, 2026, of Trodelvy for first-line unresectable locally advanced or metastatic TNBC. In the United States, Trodelvy is approved as monotherapy for patients who are not candidates for PD-1/PD-L1 inhibitor-based therapy and in combination with pembrolizumab for patients whose tumors express PD-L1 with CPS ≥10.
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