This week the U.S. Food and Drug Administration (FDA) has granted full approval to Sacituzumab Govitecan* (Trodelvy®; Gilead Sciences) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer or TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
TNBC is an aggressive type of breast cancer, accounting for approximately 15% of all breast cancers. The disease is diagnosed more frequently in younger and premenopausal women and is more prevalent in African American and Hispanic women.
One of the key characteristics of the disease is that TNBC cells do not have estrogen and progesterone receptors and have limited HER2. As a result, drugs that target these receptors, therefore, are not typically effective in treating patients diagnosed with TNBC.
Prior to the FDA approval of Sacituzumab Govitecan, patients with previously treated metastatic TNBC had few treatment options in this high unmet-need setting.
Sacituzumab govitecan, originally developed by Immunomedics, is a first-in-class antibody-drug conjugate and topoisomerase inhibitor directed to the Trop-2 receptor, a protein frequently expressed in multiple types of epithelial tumors, including TNBC, where high expression is associated with poor survival and relapse.
The drug combines a humanized monoclonal antibody with SN-38, which is conjugated to the antibody by a cleavable linker and enables delivery of high concentrations of SN-38 to tumors.
In addition to TNBC, the drug is also being developed as an investigational treatment for metastatic urothelial cancer, hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER 2-) metastatic breast cancer, and metastatic non-small cell lung cancer. And additional evaluations across multiple solid tumors are also underway.
The approval is supported by data from the Phase III ASCENT study. The study, an open-label, active-controlled, randomized confirmatory trial, enrolled more than 500 patients with relapsed/refractory metastatic TNBC who had received two or more prior systemic therapies, including a taxane, at least one of them for metastatic disease. Patients were randomized to receive either Sacituzumab Govitecan or chemotherapy chosen by the patients’ treating physicians.
In the study Sacituzumab Govitecan demonstrated a statistically significant and clinically meaningful 57% reduction in the risk of disease worsening or death or progression-free survival (PFS), extending median PFS to 4.8 months from 1.7 months with chemotherapy (HR: 0.43; 95% CI: 0.35-0.54; p<0.0001).
Sacituzumab Govitecan also extended median overall survival (OS) to 11.8 months vs. 6.9 months (HR: 0.51; 95% CI: 0.41-0.62; p<0.0001), representing a 49% reduction in the risk of death.
The FDA granted accelerated approval to Sacituzumab Govitecan in April 2020 based on objective response rate and duration of response results in a Phase I/II study. Today’s approval expands the previous Sacituzumab Govitecan indication to include treatment in adult patients with unresectable locally advanced or metastatic TNBC who have received two or more prior systemic therapies, at least one of them for metastatic disease.
“Women with triple-negative breast cancer have historically had very few effective treatment options and faced a poor prognosis,” noted Aditya Bardia, MD, MPH, Director of Breast Cancer Research Program, Mass General Cancer Center and Assistant Professor of Medicine at Harvard Medical School, and global principal investigator of the ASCENT study.
“Today’s FDA approval reflects the statistically significant survival benefit seen in the landmark ASCENT study and positions Sacituzumab Govitecan as a potential standard of care for pre-treated TNBC.”
“A metastatic TNBC diagnosis is frightening. As an aggressive and difficult-to-treat disease, it’s a significant advance to have an FDA-approved treatment option with a proven survival benefit for patients with metastatic disease that continues to progress,” added Ricki Fairley, Founder, and Chief Executive Officer of Touch, the Black Breast Cancer Alliance.
“For far too long, people with metastatic TNBC had very few treatment options. Today’s news continues the progress of bringing more options to treat this devastating disease.”
Among all patients evaluable for safety in the ASCENT study (n=482), Trodelvy had a safety profile consistent with the previously approved FDA label. The most frequent Grade ≥3 adverse reactions for Sacituzumab Govitecan compared to single-agent chemotherapy were neutropenia (52% vs. 34%), diarrhea (11% vs. 1%), leukopenia (11% vs. 6%), and anemia (9% vs. 6%). Adverse reactions leading to treatment discontinuation occurred in 5% of patients receiving Sacituzumab Govitecan.
“Today’s approval is the culmination of a multi-year development program and validates the clinical benefit of this important treatment in metastatic TNBC,” said Merdad Parsey, MD, Ph.D., Chief Medical Officer, Gilead Sciences.
“Building upon this milestone, we are committed to advancing Trodelvy with worldwide regulatory authorities so that, pending their decision, Trodelvy may become available to many more people around the world who are facing this difficult-to-treat cancer.”
Regulatory approval around the globe
Regulatory submissions for Sacituzumab Govitecan in metastatic TNBC have been filed in the United Kingdom, Canada, Switzerland, and Australia as part of Project Orbis, an initiative of the FDA Oncology Center of Excellence (OCE) that provides a framework for concurrent submission and review of oncology products among international partners, as well as in Singapore through our partner Everest Medicines.
The European Medicines Agency has also validated a Marketing Authorization Application for Sacituzumab Govitecan in the European Union. All filings are based on data from the Phase III ASCENT study.
* In the United States: Sacituzumab Govitecan-hziy
ASCENT-Study of Sacituzumab Govitecan in Refractory/Relapsed Triple-Negative Breast Cancer (ASCENT) [NCT02574455]
Highlights of prescribing information
Sacituzumab Govitecan (Trodelvy®; Gilead Sciences) [Prescribing Information]
 Bardia A, Mayer IA, Vahdat LT, Tolaney SM, Isakoff SJ, Diamond JR, O’Shaughnessy J, Moroose RL, Santin AD, Abramson VG, Shah NC, Rugo HS, Goldenberg DM, Sweidan AM, Iannone R, Washkowitz S, Sharkey RM, Wegener WA, Kalinsky K. Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2019 Feb 21;380(8):741-751. doi: 10.1056/NEJMoa1814213. PMID: 30786188.
 Syed YY. Sacituzumab Govitecan: First Approval. Drugs. 2020 Jul;80(10):1019-1025. doi: 10.1007/s40265-020-01337-5. PMID: 32529410; PMCID: PMC7288263.
Featured Image: Women and the power to fight breast cancer Courtesy: © 2017 – 2021. Fotolia/Adobe. Used with permission.