Sacituzumab govitecan (Trodelvy)

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