Gilead Sciences, Inc. announced that the European Medicines Agency (EMA) has validated a Type II variation Marketing Authorization Application (MAA) for Trodelvy(R) (sacituzumab govitecan-hziy) for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH--) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The validation of Marketing Authorization Application in pre-treated HR+/HER2- metastatic breast cancer marks an important step forward to potentially making Trodelvy available to even more patients with severely limited treatment options." This Marketing Authorization Application is based on data from the registrational Phase 3 TROPiCS-02 study, which met its primary endpoint of progression-free survival (PFS) and key secondary endpoint of overall survival (OS) versus comparator chemotherapies (treatment of physician's choice (TPC) of chemotherapy). PFS data were published in the Journal of Clinical Oncology, and OS data were recently presented at ESMO Congress 2022.

The safety profile for Trodelvy in TROPiCS-02 was consistent with prior studies, and no new safety signals were identified in this population. In October 2022, the U.S. Food and Drug Administration (FDA) accepted for priority review the supplemental Biologics License Application (sBLA) for Trodelvy for the treatment of adult patients with unresectable locally advanced or metastatic HR+/HER2-negative (IHC 0, IHC 1+ or IHC 2+/ISH--) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. The Prescription Drug User Fee Act (PDUFA) target action date is currently set for February 2023.

Trodelvy has not been approved by any regulatory agency for the treatment of HR+/HER2- metastatic breast cancer. Its safety and efficacy have not been established for this indication. Trodelvy has a Boxed Warning for severe or life-threatening neutropenia and severe diarrhea; About HR+/HER2- Metastatic Breast Cancer Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer is the most common type of breast cancer and accounts for approximately 70% of all new cases, or nearly 400,000 diagnoses worldwide each year.

Almost one in three cases of early-stage breast cancer eventually become metastatic, and among patients with HR+/HER2- metastatic disease, the five-year relative survival rate is 30%. As patients with HR+/HER2- metastatic breast cancer become resistant to endocrine-based therapy, their primary treatment option is limited to single-agent chemotherapy. In this setting, it is common to receive multiple lines of chemotherapy regimens over the course of treatment, and the prognosis remains poor.

About the TROPiCS-02 Study the TROPiCS-02 study is a global, multicenter, open-label, Phase 3 study, randomized 1:1 to evaluate Trodelvy versus physicians' choice of chemotherapy (eribulin, capecitabine, gemcitabine, or vinorelbine) in 543 patients with HR+/HER2- metastatic breast cancer who were previously treated with endocrine therapy, CDK4/6 inhibitors and two to four lines of chemotherapy for metastatic disease. The primary endpoint is progression-free survival per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review (BICR) for participants treated with Trodelvy compared to those treated with chemotherapy. Secondary endpoints include overall survival, overall response rate, clinical benefit rate and duration of response, as well as assessment of safety and tolerability and quality of life measures.

In the study, HER2 negativity was defined per American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) criteria as immunohistochemistry (IHC) score of 0, IHC 1+ or IHC 2+ with a negative in-situ hybridization (ISH) test.