Trodelvy Metastatic TNBC Approval Expands First-Line Options

The European Commission has approved Trodelvy (sacituzumab govitecan-hziy) in combination with Keytruda (pembrolizumab) for the first-line treatment of unresectable, locally advanced or metastatic triple-negative breast cancer (TNBC). The decision makes Trodelvy metastatic TNBC treatment available to adults who have not yet received systemic therapy for metastatic disease and whose tumors express PD-L1 with a combined positive score of 10 or higher (CPS ≥10).

The combination is the first and only antibody-drug conjugate (ADC) plus immunotherapy regimen approved for first-line metastatic TNBC in the European Union’s 27 member states, as well as Norway, Iceland and Liechtenstein. It follows the Commission’s earlier approval of Trodelvy monotherapy for patients in the same setting who are not candidates for PD-1 or PD-L1 inhibitor therapy. Taken together, the two approvals make Trodelvy the backbone therapy for first-line metastatic TNBC across PD-L1 status in Europe.

Trodelvy metastatic TNBC: the ASCENT-04 evidence

The approval rests on the Phase 3 ASCENT-04/KEYNOTE-D19 trial, which compared Trodelvy plus Keytruda against standard-of-care chemotherapy plus Keytruda in the first-line setting. Trodelvy cut the risk of disease progression or death by 35% in patients with PD-L1-positive metastatic TNBC, a result the company describes as highly statistically significant and clinically meaningful.

“The approval of Trodelvy plus Keytruda represents a meaningful advance in the treatment of patients with PD-L1-positive metastatic TNBC,” said Evandro de Azambuja, MD, PhD, Head of the Medical Support Team at the Jules Bordet Institute and an investigator of the ASCENT-04 study. “This regimen helps redefine a standard of care by offering a novel first-line treatment option for a metastatic patient population with a particularly aggressive form of breast cancer.”

Why first-line treatment matters

TNBC is the most aggressive form of breast cancer and makes up roughly 15% of all breast cancers. It disproportionately affects younger, premenopausal, and Black and Hispanic women. The cells lack estrogen and progesterone receptors and show limited HER2 expression, which leaves far fewer treatment options than other breast cancer subtypes.

The disease also returns sooner and is more often fatal once it spreads. The average time to metastatic recurrence for TNBC is about 2.6 years, compared with five years for other breast cancers. Among women with metastatic TNBC, the five-year survival rate is 12%, versus 28% for other types of metastatic breast cancer.

A broader Trodelvy franchise

Trodelvy is a first-in-class Trop-2-directed ADC. Trop-2 is expressed in more than 90% of breast and lung cancers, and the drug pairs a proprietary hydrolyzable linker with SN-38, a topoisomerase I inhibitor, to deliver activity both to Trop-2-expressing cells and to the surrounding tumor microenvironment through a bystander effect.

“Today’s approval transforms the treatment landscape for all patients with first-line metastatic TNBC,” said Mika Kakefuda Derynck, MD, Senior Vice President, Clinical Development, Oncology at Gilead Sciences. “With Trodelvy-based options now approved in the EU for all eligible first-line metastatic TNBC patients across PD-L1 status, we have established a new, much-needed backbone therapy.”

The US FDA and the European Commission have both approved Trodelvy alone or in combination with pembrolizumab for first-line metastatic TNBC, and the drug is also approved globally for second-line and later metastatic TNBC and for pre-treated HR+/HER2- metastatic breast cancer. Gilead reports clinical experience in more than 75,000 breast cancer patients since 2020. It is the only ADC with four positive Phase 3 trials in HER2-negative metastatic breast cancer and the only Trop-2-directed ADC to show a meaningful overall survival benefit in two distinct types of metastatic breast cancer.

Source: Gilead Sciences press release, 24 August 2026.