Sacituzumab govitecan


Sacituzumab govitecan, sold under the brand name Trodelvy, is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate for the treatment of adults with triple-negative breast cancer that has spread to other parts of the body and have received at least two prior therapies.
The most common side effects are nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia, constipation, decreased appetite, rash and abdominal pain.
Sacituzumab govitecan has a boxed warning about the risk of severe neutropenia and severe diarrhea.
Sacituzumab govitecan may cause harm to a developing fetus or newborn baby.

Mechanism

It is a conjugate of the humanized anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan. Each antibody having on average 7.6 molecules of SN-38 attached. SN-38 is too toxic to administer directly to patients, but linkage to an antibody allows the drug to specifically target cells containing Trop-2.
Sacituzumab govitecan is a Trop-2-directed antibody and topoisomerase inhibitor drug conjugate, meaning that the drug targets the Trop-2 receptor that helps the cancer grow, divide and spread, and is linked to topoisomerase inhibitor, which is a chemical compound that is toxic to cancer cells. Approximately two of every ten breast cancer diagnoses worldwide are triple-negative. Triple-negative breast cancer is a type of breast cancer that tests negative for estrogen receptors, progesterone receptors and human epidermal growth factor receptor 2 protein. Therefore, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2.

Development

Immunomedics announced in 2013, that it had received fast track designation from the US Food and Drug Administration for the compound as a potential treatment for non-small cell lung cancer, small cell lung cancer, and metastatic triple-negative breast cancer. Orphan drug status was granted for small cell lung cancer and pancreatic cancer. In February 2016, Immunomedics announced that sacituzumab govitecan had received an FDA breakthrough therapy designation for the treatment of patients with triple-negative breast cancer who have failed at least two other prior therapies for metastatic disease.

History

Sacituzumab govitecan was added to the proposed INN list in 2015, and to the recommended list in 2016.
Sacituzumab govitecan-hziy was approved for use in the United States in April 2020.
Sacituzumab govitecan-hziy was approved based on the results of IMMU-132-01, a multicenter, single-arm clinical trial of 108 subjects with metastatic triple-negative breast cancer who had received at least two prior treatments for metastatic disease. Subjects received sacituzumab govitecan-hziy 10 mg/kg intravenously on days one and eight every 21 days. Tumor imaging was obtained every eight weeks, and patients were treated until disease progression or intolerance to therapy. The efficacy of sacituzumab govitecan-hziy was based on the overall response rate – which reflects the percentage of subjects that had a certain amount of tumor shrinkage. The ORR was 33.3%, with a median duration of response of 7.7 months. Of the subjects with a response to sacituzumab govitecan-hziy, 55.6% maintained their response for six or more months and 16.7% maintained their response for twelve or more months.
Sacituzumab govitecan-hziy was granted accelerated approval along with priority review, breakthrough therapy, and fast track designations. The U.S. Food and Drug Administration granted approval of Trodelvy to Immunomedics, Inc.