FDA Accepts Sacituzumab Govitecan-hziy for Priority Review in Pre-Treated HR+/HER2- Metastatic Breast Cancer

In a trial, sacituzumab govitecan-hziy demonstrated a 34% reduction in the risk of disease progression or death compared with physician’s choice chemotherapy.

The FDA has accepted Gilead’s sacituzumab govitecan-hziy (Trodelvy) for priority review in the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting.

Priority Review is granted for therapies that would be significant improvements in the safety or efficacy of the treatment, diagnosis, or prevention of serious conditions if they were approved. The Prescription Drug User Fee Act (PDUFA) target action date is currently February 2023.

The supplemental Biologics License Application is based on data from the registrational phase 3 TROPiCS-02 study, which met the primary endpoint of progression-free survival (PFS) and the key secondary endpoint of overall survival (OS) over comparator chemotherapy. According to the study, sacituzumab govitecan-hziy demonstrated a 34% reduction in the risk of disease progression or death and a 21% decrease in the risk of death compared to physician’s choice treatment.

“Trodelvy has already changed the treatment landscape in second-line metastatic triple-negative breast cancer (TNBC) and pre-treated metastatic urothelial cancer, and today’s news marks our third supplemental application acceptance within the last two years,” said Bill Grossman, MD, PhD, senior vice president and therapeutic area head at Gilead Oncology, in a press release.

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 bladder cancers. Sacituzumab govitecan-hziy is also designed with a proprietary hydrolysable linker attached to SN-38, a topoisomerase I inhibitor payload. This combination allows it to deliver potent activity to both Trop-2 expressing cells and the microenvironment.

The safety profile in the TROPiCS-02 trial was consistent with prior studies, with no new safety concerns identified in the patient population.

Sacituzumab govitecan-hziy is also being developed for potential investigational use in TNBC and metastatic urothelial cancer populations, as well as a range of tumor types for which Trop-2 is highly expressed, including HR+/HER2- metastatic breast cancer, metastatic non-small cell lung cancer, metastatic small cell lung cancer, head and neck cancer, and endometrial cancer.

Sacituzumab govitecan-hziy is currently included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology. This includes a category 1 recommendation for use in adults with second-line metastatic TNBC and a category 2A preferred recommendation for investigational use in HR+/HER2- advanced breast cancer after prior treatment including endocrine therapy, a CDK4/6 inhibitor, and at least 2 lines of chemotherapy based on the PFS data from the TROPiCS-02 trial. NCCN Guidelines also have a category 2A recommendation for use in locally advanced or metastatic bladder cancer after prior treatment with platinum and a checkpoint inhibitor.

“People with pre-treated HR+/HER2- metastatic breast cancer who have progressed on endocrine-based therapies and chemotherapy have limited treatment options, and we look forward to working with the FDA to potentially make Trodelvy available to patients who need it most,” Grossman said in the press release.


US FDA Accepts for Priority Review the Supplemental Biologics License Application for Gilead’s Trodelvy for Pre-Treated HR+/HER2- Metastatic Breast Cancer. News release. Gilead; October 11, 2022. Accessed October 11, 2022. https://www.gilead.com/news-and-press/press-room/press-releases/2022/10/us-fda-accepts-for-priority-review-the-supplemental-biologics-license-application-for-gileads-trodelvy-for-pretreated-hrher2-metastatic-breast