Regulatory & Policy

Trodelvy stakes out broader first-line TNBC role with EU combo approval

Trodelvy stakes out broader first-line TNBC role with EU combo approval

The European Commission has approved Trodelvy (sacituzumab govitecan) in combination with pembrolizumab for adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have not received prior systemic therapy for metastatic disease and whose tumors express PD-L1 with a combined positive score (CPS ≥10). The decision makes the regimen the first antibody-drug conjugate (ADC) plus immunotherapy combination approved in first-line metastatic TNBC across the EU's 27 member states, Norway, Iceland, and Liechtenstein.

The combination approval follows a recent EC decision permitting Trodelvy monotherapy for first-line metastatic TNBC patients who are not candidates for PD-1 or PD-L1 inhibitor therapy. Together, Gilead Sciences (Nasdaq: GILD) said, the two approvals position Trodelvy as the backbone treatment for first-line metastatic TNBC regardless of PD-L1 status in Europe.

The combination approval is based on the Phase III ASCENT-04/KEYNOTE-D19 trial, which evaluated Trodelvy plus pembrolizumab against standard-of-care chemotherapy plus pembrolizumab as first-line treatment in PD-L1-positive metastatic TNBC. The study reported a statistically significant improvement in progression-free survival, with Trodelvy demonstrating a 35% reduced risk of disease progression or death compared with the chemotherapy-based control arm, Gilead said.

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Trodelvy targets Trop-2, a cell surface antigen highly expressed across multiple tumor types, using a hydrolyzable linker to deliver SN-38, a topoisomerase I inhibitor payload. The design enables cytotoxic activity in Trop-2-expressing cells and in adjacent tumor cells through a bystander effect; this is combined with pembrolizumab's PD-1 checkpoint blockade.

The EU approval broadens competition among TROP2-directed ADCs in first-line metastatic TNBC. Datroway, developed by AstraZeneca and Daiichi Sankyo, was approved in July 2026 for patients who are not candidates for PD-1/PD-L1 inhibitor therapy, while Trodelvy now spans both PD-L1-positive patients eligible for pembrolizumab and patients unsuitable for checkpoint inhibition. Further competitive pressure may emerge from sacituzumab tirumotecan, a next-generation TROP2 ADC from Kelun-Biotech and Merck & Co., which met its primary endpoint in a Phase III first-line TNBC trial. Notably, the same Trodelvy plus pembrolizumab combination did not succeed in non-small cell lung cancer. Gilead has indicated US FDA decisions on Trodelvy in first-line metastatic TNBC, based on the ASCENT-03 and ASCENT-04 trials, are anticipated.


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