European Commission Expands Role of Gilead’s Trodelvy® in First-Line Metastatic Triple-Negative Breast Cancer Across PD-L1 Status
Gilead Sciences, Inc. announced that the European Commission (EC) has granted marketing authorization for Trodelvy® (sacituzumab govitecan-hziy) in combination with Keytruda® (pembrolizumab) for the treatment of 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).
Trodelvy plus Keytruda is the first and only antibody-drug conjugate (ADC) plus immunotherapy combination to be approved in first-line metastatic TNBC in the European Union’s 27 member states, as well as Norway, Iceland and Liechtenstein.
This decision follows the recent EC approval of Trodelvy as monotherapy for the treatment of adult patients with unresectable locally advanced or metastatic TNBC who have not received prior systemic therapy for metastatic disease and are not candidates for PD-1 or PD-L1 inhibitor therapy. Together, these approvals establish Trodelvy as the backbone therapy for patients with first-line metastatic TNBC across PD-L1 status in Europe. This decision provides a new treatment option for the most aggressive form of breast cancer at the first sign of metastatic disease.
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, Jules Bordet Institute and 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.
The approval is based on data from the Phase 3 ASCENT-04 /KEYNOTE-D19 study which demonstrated a highly statistically significant and clinically meaningful progression-free survival of Trodelvy plus Keytruda versus the combination of standard of care chemotherapy plus Keytruda as a first-line treatment. In ASCENT-04/KEYNOTE-D19, Trodelvy demonstrated a 35% reduced risk of disease progression or death in patients with PD-L1-positive metastatic TNBC.
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. This is an important milestone for patients who need new options earlier in their treatment journey.”
Metastatic TNBC has historically been difficult to treat, with a poor prognosis and an urgent need for more effective first-line options. With today’s approval, Trodelvy is now positioned to address this need across the full spectrum of the disease, building on its extensive clinical legacy in later lines of therapy and its established safety and efficacy profile in more than 75,000 patients treated globally.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC., a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
About Triple-Negative Breast Cancer
TNBC is the most aggressive type of breast cancer and has historically been difficult to treat, accounting for approximately 15% of all breast cancers. TNBC disproportionally impacts younger, premenopausal, and Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited HER2 expression. Due to the nature of TNBC, treatment options are extremely limited compared with other breast cancer types.
TNBC has a higher chance of recurrence and metastases than other breast cancer types. The average time to metastatic recurrence for TNBC is approximately 2.6 years compared with 5 years for other breast cancers, and the relative five-year survival rate is much lower. Among women with metastatic TNBC, the five-year survival rate is 12%, compared with 28% for those with other types of metastatic breast cancer.
About Trodelvy
Trodelvy (sacituzumab govitecan-hziy) is a first-in-class Trop-2-directed antibody-drug conjugate. Trop-2 is a cell surface antigen highly expressed in multiple tumor types, including in more than 90% of breast and lung cancers. Trodelvy is intentionally designed with a proprietary hydrolyzable linker attached to SN-38, a topoisomerase I inhibitor payload. This unique combination delivers potent activity to both Trop-2 expressing cells and the tumor microenvironment through a bystander effect.
The U.S. FDA and the European Commission have approved the use of Trodelvy alone or in combination with pembrolizumab in first-line metastatic TNBC, across PD-L1 status. It is also globally approved for second-line and later metastatic TNBC and pre-treated HR+/HER2- metastatic breast cancer.
Healthcare professionals have substantial clinical experience with Trodelvy, with more than 75,000 breast cancer patients treated 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 demonstrate a meaningful overall survival benefit in two distinct types of metastatic breast cancer.
Trodelvy is currently being evaluated in multiple ongoing Phase 3 trials across a range of tumor types with high Trop-2 expression, including in lung and gynecologic cancers, where previous proof-of-concept studies have demonstrated clinical activity.
