Sacituzumab-Govitecan

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Structural formula
No drawing available
General
Non-proprietary name Sacituzumab govitecan
other names
  • IMMU-132
  • hRS7-CL2A-SN-38
Molecular formula
  • C 6496 H 9986 N 1702 O 2016 S 42  (sacituzumab)
  • C 73 H 98 N 11 O 22 (Govitecan)
External identifiers / databases
CAS number 1491917-83-9
PubChem 91668186
DrugBank DB12893
Wikidata Q23901469
Drug information
Drug class

Cytostatic , monoclonal antibody

Mechanism of action

Topoisomerase inhibitor

properties
Molar mass approx. 160 kD
safety instructions
GHS hazard labeling
no classification available
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

The antineoplastic component SN-38 (7-ethyl-10-hydroxycamptothecin) is the active metabolite of irinotecan

Sacituzumab govitecan (also spelled sacituzumab govitecan ) is a drug used for the parenteral treatment of breast cancer . It was approved in the United States in 2020 under the name Trodelvy .

properties

Sacituzumab-Govitecan is an antibody-drug conjugate of the third generation and accordingly consists of three components:

The monoclonal antibody is produced recombinantly in cell cultures of murine myeloma cells , while the low molecular weight components SN-38 and CL2A are produced by chemical synthesis. In sacituzumab-govitecan there is an average of 7 to 8 molecules of SN-38 for one antibody molecule. SN-38 can not be administered directly to patients due to its toxicity and poor solubility. The end of the word -tecan in the substance name is generally used for antineoplastic topoisomerase I inhibitors that are chemically derived from campothecin.

Working principle

Pharmacological data suggest that sacituzumab-govitecan binds to trop-2-expressing cancer cells and then, after internalization, releases the SN-38 by hydrolysis of the linker. SN-38 interacts with topoisomerase I and prevents re- ligation of topoisomerase I-induced single-strand breaks . The resulting DNA damage leads to apoptosis and cell death.

The most common adverse effects, seen in more than 25 percent of patients, are neutropenia and diarrhea (which can also be severe), nausea, fatigue, anemia , vomiting, alopecia , constipation, rash, decreased appetite, and abdominal pain.

Indications

Sacituzumab-Govitecan is indicated for the treatment of metastatic triple negative breast cancer ( triple-negative breast cancer , TNBC) in adults who have undergone at least two previous therapies. Triple negative breast cancer, which is diagnosed in about 15% to 20% of breast cancers, is characterized by a lack of estrogen and progesterone receptor expression and low HER2 expression and is not accessible to either antihormonal therapy or targeted HER2 blockade. The tumors have a high rate of proliferation and occur mainly in young women. TNBC has a poor prognosis and is difficult to treat.

development

Sacituzumab-Govitecan ( Trodelvy ) was developed by Immunomedics, Inc (USA). After the preclinical studies initiated in 2007, the clinical phase began in 2013. As a candidate for the treatment of serious or life-threatening diseases, the drug acquired some special FDA procedures such as fast track designation (2015), breakthrough therapy designation (2016) and priority review (2018). Approval was granted in April 2020 according to an accelerated approval program . It is based on the results of the multicenter, single-arm clinical study IMMU-132-01 in 108 patients with metastatic triple negative breast cancer who had already received at least two antimetastatic treatments. The assessment of efficacy was based on the overall response rate (ORR), which was 33.3%, and the duration of the response. H. the duration of the response in the patients who had responded to the therapy (in 55.6% it was at least 6 months, in 16.7% at least 12 months, on average 7.7 months).

For the treatment of small cell lung cancer and pancreatic cancer , orphan drug status was granted in the USA in 2013 .

Individual evidence

  1. ↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
  2. ↑ External identifiers or database links for 7-ethyl-10-hydroxycamptothecin : CAS number: 86639-52-3, EC number: 643-093-9, ECHA InfoCard: 100.171.154 , PubChem : 104842 , ChemSpider : 94634 , DrugBank : DB05482 , Wikidata : Q1750127 . Molecular formula: C 22 H 20 N 2 O 5 .
  3. ↑ Novel Drug Approvals for 2020 . FDA .
  4. ↑ a b c d e TRODELVY- sacituzumab govitecan powder, for solution (PDF) . FDA., April 2020
  5. ↑ Neelesh K. Mehra: Multifunctional carbon nanotubes in cancer therapy and imaging , In: Nanobiomaterials in Medical Imaging, 2016th
  6. ↑ The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances ( PDF ), “Stem-Book 2018” of the WHO.
  7. ↑ DM Goldenberg, RM Sharkey: Sacituzumab Govitecan, a Novel, Third-Generation, Antibody-Drug Conjugate (ADC) for Cancer Therapy In: Expert Opin Biol Ther. 2020 , doi : 10.1080 / 14712598.2020.1757067 . PMID 32301634 .
  8. ↑ What exactly is triple negative breast cancer or triple negative breast cancer? , mammazentrum-hamburg.de, accessed on June 30, 2020.
  9. ↑ YY Syed: Sacituzumab Govitecan: First Approval . Drugs, Volume 80 (2020), pp. 1019-1025, doi: 10.1007 / s40265-020-01337-5 .
  10. ↑ Entry in the FDA Orphan Register , accessed on July 1, 2020.