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 (TNBC) that has spread to other parts of the body and have received at least two prior therapies.[1][2]

Sacituzumab govitecan
Monoclonal antibody
Type?
SourceHumanized (from mouse)
TargetTrop-2
Clinical data
Trade namesTrodelvy
Other namesIMMU-132, hRS7-SN-38, sacituzumab govitecan-hziy
AHFS/Drugs.comTrodelvy
License data
Pregnancy
category
  • Contraindicated
ATC code
  • none
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC76H104N12O24S
Molar mass1601.8 g·mol−1
3D model (JSmol)

The most common side effects are nausea, neutropenia, diarrhea, fatigue, anemia, vomiting, alopecia (hair loss), constipation, decreased appetite, rash and abdominal pain.[1][2]

Sacituzumab govitecan has a boxed warning about the risk of severe neutropenia (abnormally low levels of white blood cells) and severe diarrhea.[1][2]

Sacituzumab govitecan may cause harm to a developing fetus or newborn baby.[1]

Mechanism

It is a conjugate of the humanized anti-Trop-2 monoclonal antibody linked with SN-38, the active metabolite of irinotecan.[3] Each antibody having on average 7.6 molecules of SN-38 attached.[4] 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.[1] Approximately two of every ten breast cancer diagnoses worldwide are triple-negative.[1] 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 (HER2) protein.[1] Therefore, triple-negative breast cancer does not respond to hormonal therapy medicines or medicines that target HER2.[1]

Development

Immunomedics announced in 2013, that it had received fast track designation from the US Food and Drug Administration (FDA) 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.[5][6] In February 2016, Immunomedics announced that sacituzumab govitecan had received an FDA breakthrough therapy designation (a classification designed to expedite the development and review of drugs that are intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition) for the treatment of patients with triple-negative breast cancer who have failed at least two other prior therapies for metastatic disease.[7][8]

History

Sacituzumab govitecan was added to the proposed INN list in 2015,[9] and to the recommended list in 2016.[10]

Sacituzumab govitecan-hziy was approved for use in the United States in April 2020.[1][11][12][2]

Sacituzumab govitecan-hziy was approved based on the results of IMMU-132-01, a multicenter, single-arm clinical trial (NCT01631552) of 108 subjects with metastatic triple-negative breast cancer who had received at least two prior treatments for metastatic disease.[1][12][2] Subjects received sacituzumab govitecan-hziy 10 mg/kg intravenously on days one and eight every 21 days.[12] Tumor imaging was obtained every eight weeks, and patients were treated until disease progression or intolerance to therapy.[12][2] The efficacy of sacituzumab govitecan-hziy was based on the overall response rate (ORR) – which reflects the percentage of subjects that had a certain amount of tumor shrinkage.[1][12] The ORR was 33.3%, with a median duration of response of 7.7 months.[1][12] 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.[1][12]

Sacituzumab govitecan-hziy was granted accelerated approval along with priority review, breakthrough therapy, and fast track designations.[1][12] The U.S. Food and Drug Administration (FDA) granted approval of Trodelvy to Immunomedics, Inc.[1]

References
  1. "FDA Approves New Therapy for Triple Negative Breast Cancer That Has Spread, Not Responded to Other Treatments". U.S. Food and Drug Administration (FDA). 22 April 2020. Retrieved 22 April 2020. This article incorporates text from this source, which is in the public domain.
  2. "Drug Trial Snapshot: Trodelvy". U.S. Food and Drug Administration (FDA). 22 April 2020. Retrieved 29 April 2020. This article incorporates text from this source, which is in the public domain.
  3. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. 2015
  4. "Novel Agents are Targeting Drivers of TNBC". www.medpagetoday.com. 28 June 2016.
  5. "Sacituzumab govitecan Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 22 April 2020.
  6. "Sacituzumab govitecan Orphan Drug Designation and Approval". U.S. Food and Drug Administration (FDA). 24 December 1999. Retrieved 22 April 2020.
  7. "New Therapy Shows Early Promise, Continues to Progress in Triple-Negative Breast Cancer". Cure Today.
  8. "U.S. Food and Drug Administration (FDA) Grants Breakthrough Therapy Designation to Immunomedics for Sacituzumab Govitecan for the Treatment of Patients With Triple-Negative Breast Cancer" (Press release). Immunomedics. 5 February 2016. Retrieved 25 April 2020 – via GlobeNewswire.
  9. World Health Organization (2015). "International nonproprietary names for pharmaceutical substances (INN): proposed INN: list 113". WHO Drug Information. 29 (2): 260–1. hdl:10665/331080.
  10. World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 75". WHO Drug Information. 30 (1): 151–3. hdl:10665/331046.
  11. "Trodelvy: FDA-Approved Drugs". U.S. Food and Drug Administration (FDA). Retrieved 22 April 2020.
  12. "FDA grants accelerated approval to sacituzumab govitecan-hziy for metastatic triple negative breast cancer". U.S. Food and Drug Administration (FDA). 22 April 2020. Retrieved 23 April 2020. This article incorporates text from this source, which is in the public domain.

Further reading
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.