Gilead Sciences, Inc. announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for sacituzumab govitecan as monotherapy indicated for adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who have received two or more prior systemic therapies, at least one of them for advanced disease. The final European Commission decision on the Marketing Authorization Application for sacituzumab govitecan is anticipated later in 2021. TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. It is more frequently diagnosed in younger and premenopausal women and is more prevalent in Black and Hispanic women. The five-year survival rate for this sub-type is 12%, compared with 28% for other breast cancer types, and these poor outcomes are often coupled with a significant decrease in quality of life, especially in relapsed/refractory disease. Sacituzumab govitecan is a first-in-class Trop-2 directed antibody-drug conjugate. Trop-2 is a protein located on the surface of cells and is overexpressed in TNBC and many other tumors. The positive opinion is supported by results from the Phase 3 ASCENT study, where sacituzumab govitecan showed a statistically significant and clinically meaningful 57% reduction in the risk of disease worsening or death and improved median progression-free survival (PFS) to 4.8 months from 1.7 months seen with physician’s choice of chemotherapy alone among all randomized patients, which included those with and without brain metastases (HR: 0.43; 95% CI: 0.35-0.54; p<0.0001). Sacituzumab govitecan also reduced the risk of death by 49% and improved median overall survival to 11.8 months vs. 6.9 months with physician’s choice of chemotherapy (HR: 0.51; 95% CI: 0.41-0.62; p<0.0001). The most common Grade 3 or higher adverse reactions were neutropenia (49.5%), leukopenia (12.0%), diarrhea (10.7%), anemia (10.1%), febrile neutropenia (6.6%), fatigue (5.2%), hypophosphatemia (5.2%), nausea (4.1%) and vomiting (3.0%). The sacituzumab govitecan U.S. Prescribing Information has a BOXED WARNING for severe or life-threatening neutropenia and severe diarrhea; see below for Important Safety Information. Sacituzumab govitecan (under the trade name Trodelvy®) is approved in Australia, Canada, Great Britain, Switzerland, and the United States in metastatic TNBC, and review is also underway in Singapore and China through Everest Medicines. The ASCENT study is a global, open-label, randomized Phase 3 study that enrolled more than 500 patients across 230 study locations. The study evaluated the efficacy and safety of sacituzumab govitecan compared with a single-agent chemotherapy of the physician’s choice in patients with unresectable, locally advanced or metastatic TNBC who had received at least two prior systemic treatments. Patients were randomly allocated to receive either sacituzumab govitecan or a chemotherapy chosen by the patient’s treating physician. The primary endpoint was progression-free survival (PFS, as determined by blinded independent central review) in patients without brain metastases. Secondary endpoints included: PFS for full study population or intention-to-treat (ITT) population, overall survival in both the ITT population and in the subgroup without brain metastasis, independently determined objective response rate, duration of response, time to onset of response according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), quality of life and safety. TNBC is the most aggressive type of breast cancer and accounts for approximately 15% of all breast cancers. TNBC is diagnosed more frequently in younger and premenopausal women and is more prevalent in Black and Hispanic women. TNBC cells do not have estrogen and progesterone receptors and have limited human epidermal growth factor receptor 2 (HER2). Due to the nature of TNBC, effective 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. Sacituzumab govitecan is a first-in-class antibody and topoisomerase inhibitor conjugate directed to the Trop-2 receptor, a protein overexpressed in multiple types of epithelial tumors, including metastatic TNBC and metastatic urothelial cancer (UC), where high expression is associated with poor survival and relapse. Beyond the approvals of sacituzumab govitecan in the United States, it is also approved for metastatic TNBC in Australia, Canada, Great Britain and Switzerland for adults with metastatic TNBC. Sacituzumab govitecan is also under multiple regulatory reviews worldwide, including the EU, as well as in Singapore and China through partner Everest Medicines. Sacituzumab govitecan continues to be developed for potential use in other TNBC and metastatic UC populations and is also being developed as an investigational treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer and metastatic non-small cell lung cancer. Additional evaluation across multiple solid tumors is also underway.