Difference between revisions of "Sacituzumab govitecan (Trodelvy)"

Latest revision as of 00:24, 23 September 2023

Mechanism of action

From the NCI Drug Dictionary: An antibody-drug conjugate containing the humanized monoclonal antibody, hRS7, against tumor-associated calcium signal transducer 2 (TACSTD2 or TROP2) and linked to the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), with potential antineoplastic activity. The antibody moiety of sacituzumab govitecan selectively binds to TROP2. After internalization and proteolytic cleavage, SN-38 selectively stabilizes topoisomerase I-DNA covalent complexes, resulting in DNA breaks that inhibit DNA replication and trigger apoptosis.

Diseases for which it is established

History of changes in FDA indication

Breast cancer

2020-04-22: Granted accelerated approval for adult patients with metastatic triple-negative breast cancer who received at least two prior therapies for metastatic disease. (Based on IMMU-132-01)
- 2021-04-07: Granted regular approval for patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. (Based on ASCENT)
2023-02-03: Approved for unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) breast cancer who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. (Based on TROPiCS-02)

Urothelial carcinoma

2021-04-13: Granted accelerated approval for patients with locally advanced or metastatic urothelial cancer (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor. (Based on TROPHY-U-01)

History of changes in EMA indication

2021-11-22: Initial marketing authorization as Trodelvy. Trodelvy as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. (Based on ASCENT)
2023-07-26: Extension of indication to include treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting. (Based on TROPiCS-02)

History of changes in Health Canada indication

2021-09-24: Initial notice of compliance for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (mTNBC) who have received two or more prior therapies, at least one of them for metastatic disease.

Also known as

Code names: IMMU-132, RS7-SN38
Generic name: sacituzumab govitecan-hziy
Brand name: Trodelvy

@@ Line 1: / Line 1: @@
 ==Mechanism of action==
 From the [https://www.cancer.gov/publications/dictionaries/cancer-drug?cdrid=736415 NCI Drug Dictionary]: An antibody-drug conjugate containing the humanized monoclonal antibody, hRS7, against tumor-associated calcium signal transducer 2 (TACSTD2 or TROP2) and linked to the active metabolite of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN-38), with potential antineoplastic activity. The antibody moiety of sacituzumab govitecan selectively binds to TROP2. After internalization and proteolytic cleavage, SN-38 selectively stabilizes topoisomerase I-DNA covalent complexes, resulting in DNA breaks that inhibit DNA replication and trigger apoptosis.
+==Diseases for which it is established==
+*[[Breast cancer, ER-positive|HR+ breast cancer]]
+*[[Breast_cancer,_triple_negative|TNBC]]
+*[[Urothelial carcinoma]]
+==History of changes in FDA indication==
+===[[Breast cancer]]===
+*2020-04-22: Granted accelerated approval for adult patients with metastatic triple-negative [[breast cancer]] who received at least two prior therapies for metastatic disease. ''(Based on IMMU-132-01)''
+**2021-04-07: Granted regular approval for patients with unresectable locally advanced or metastatic triple-negative [[breast cancer]] (mTNBC) who have received two or more prior systemic therapies, at least one of them for metastatic disease. ''(Based on ASCENT)''
+*2023-02-03: Approved for unresectable locally advanced or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative (IHC 0, IHC 1+ or IHC 2+/ISH-) [[breast cancer]] who have received endocrine-based therapy and at least two additional systemic therapies in the metastatic setting. ''(Based on TROPiCS-02)''
+===[[Urothelial carcinoma]]===
+*2021-04-13: Granted accelerated approval for patients with locally advanced or metastatic [[Urothelial carcinoma|urothelial cancer]] (mUC) who previously received a platinum-containing chemotherapy and either a programmed death receptor-1 (PD-1) or a programmed death-ligand 1 (PD-L1) inhibitor. ''(Based on TROPHY-U-01)''
-==Preliminary data==
+==History of changes in EMA indication==
-===[[Breast_cancer,_triple_negative|TNBC]]===
+*2021-11-22: Initial marketing authorization as Trodelvy. Trodelvy as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic triple-negative [[breast cancer]] (mTNBC) who have received two or more prior systemic therapies, including at least one of them for advanced disease. ''(Based on ASCENT)''
-* Bardia A, Mayer IA, Diamond JR, Moroose RL, Isakoff SJ, Starodub AN, Shah NC, O'Shaughnessy J, Kalinsky K, Guarino M, Abramson V, Juric D, Tolaney SM, Berlin J, Messersmith WA, Ocean AJ, Wegener WA, Maliakal P, Sharkey RM, Govindan SV, Goldenberg DM, Vahdat LT. Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017 Jul 1;35(19):2141-2148. Epub 2017 Mar 14. [https://ascopubs.org/doi/full/10.1200/JCO.2016.70.8297 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28291390 PubMed]
+*2023-07-26: Extension of indication to include treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative [[breast cancer]] who have received endocrine-based therapy, and at least two additional systemic therapies in the advanced setting. ''(Based on TROPiCS-02)''
-===[[Non-small cell lung cancer]]===
+==History of changes in Health Canada indication==
-* Heist RS, Guarino MJ, Masters G, Purcell WT, Starodub AN, Horn L, Scheff RJ, Bardia A, Messersmith WA, Berlin J, Ocean AJ, Govindan SV, Maliakal P, Mudenda B, Wegener WA, Sharkey RM, Goldenberg DM, Camidge DR. Therapy of Advanced Non-Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan. J Clin Oncol. 2017 Aug 20;35(24):2790-2797. Epub 2017 May 26. [https://ascopubs.org/doi/full/10.1200/JCO.2016.72.1894 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28548889 PubMed]
+*2021-09-24: Initial notice of compliance for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative [[breast cancer]] (mTNBC) who have received two or more prior therapies, at least one of them for metastatic disease.
 ==Also known as==
-*'''Code name:''' RS7-SN38
+*'''Code names:''' IMMU-132, RS7-SN38
+*'''Generic name:''' sacituzumab govitecan-hziy
+*'''Brand name:''' Trodelvy
 [[Category:Drugs]]
 [[Category:Intravenous medications]]
+[[Category:Anti-TACSTD2 antibody-drug conjugates]]
+[[Category:Topoisomerase I inhibitors]]
-[[Category:Antibody-drug conjugates]]
+[[Category:Breast cancer medications]]
-[[Category:Anti-TACSTD2 antibodies]]
+[[Category:Urothelial carcinoma medications]]
-[[Category:Topoisomerase inhibitors]]
-[[Category:Investigational drugs]]
+[[Category:EMA approved in 2021]]
+[[Category:FDA approved in 2020]]
+[[Category:Health Canada approved in 2021]]