Sacituzumab govitecan (Trodelvy) in combination with pembrolizumab (Keytruda) has received a CHMP positive opinion for first-line treatment of PD-L1-positive metastatic triple-negative breast cancer, a move that would position the Trop-2-directed antibody-drug conjugate as a backbone therapy across PD-L1 status in the EU — covering both patients eligible for checkpoint inhibition and, through a prior monotherapy approval, those who are not. For a disease where approximately 40% of metastatic tumors express PD-L1 and five-year survival sits at 12%, the combination addresses the subset with the greatest urgency for effective first-line intervention.
The CHMP's recommended indication covers adult patients 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 of 10 or greater. Pembrolizumab is a product of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co. An European Commission marketing authorization decision is anticipated later in 2026.
The CHMP recommendation is based on the Phase III ASCENT-04/KEYNOTE-D19 trial, which compared sacituzumab govitecan plus pembrolizumab against standard-of-care chemotherapy plus pembrolizumab in previously untreated PD-L1-positive metastatic TNBC patients. The primary endpoint was progression-free survival. The combination reported a 35% reduction in the risk of disease progression or death versus the chemotherapy backbone, a result described as highly statistically significant and clinically meaningful. The trial used a crossover design that allowed patients in the control arm to receive sacituzumab govitecan after progression, reflecting an intent to isolate the contribution of the ADC to the pembrolizumab platform rather than deny patients access to it.
Sacituzumab govitecan is a first-in-class Trop-2-directed ADC. Trop-2 is highly expressed across multiple tumor types, including more than 90% of breast cancers. The construct uses a hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor, enabling payload delivery both to Trop-2-expressing cells and to neighboring cells in the tumor microenvironment through a bystander effect — a feature that may be relevant in heterogeneous tumors where antigen expression varies across lesions.