Synonyms: ado-trastuzumab emtansine | Kadcyla® | PRO-132365 | RG-3502

trastuzumab emtansine is an approved drug (EMA and FDA (2013))

Compound class: Antibody

Comment: Trastuzumab emtansine is a antibody-drug conjugate (ADC) containing a targeting antibody (anti-erbB2) conjugated to a cytotoxic drug (mertansine or DM1) [4]. The PubChem CID for the mertasine component compound is CID 11343137. Mertansine (or DM1) is a macrolide of the ansamycin type and can be isolated from plants of the genus Maytenus. It is known as a maytansinoid. This agent binds to the rhizoxin binding site on β-tubulin and functions in a similar fashion to the Vinca alkaloids.
Annotated peptide sequences for this antibody are available from its IMGT/mAb-DB record.

Other trastuzumab-based antibody-drug conjugates (ADCs):
trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki, DS-8201, Enhertu®; Daiichi Sankyo) delivers a topoisomerase I inhibitor payload [6-7]. It progressed through clinical development and received FDA approval in December 2019 as a treatment for metastatic breast cancer, and EMA authorisation for this indication followed in early 2021. Based on results from the DESTINY-Lung02 trial (NCT04644237) that demonstrated efficacy in patients with HER2 mutation-positive, unresectable/metastatic non-small cell lung cancer (NSCLC), Enhertu® was FDA approved as the first therapeutic for this type of NSCLC in August 2022.
trastuzumab duocarmazine (SYD985, a.k.a. trastuzumab vc-seco-DUBA, [vic-]trastuzumab duocarmazine; Synthon/Byondis) [2] delivers the highy cytotoxic DNA methylating pro-drug, seco-duocarmycinhydroxybenzamide- azaindole, to HER2-expressing cancer cells [5,7]. The payload is conjugated to the antibody via a linker that is cleaved once the ADC is internalised by cancer cells, and the pro-drug is then metabolised to the active toxin. SYD985 was granted fast track designation by the FDA in early 2018, based on positive phase 1 data [1]. This agent is in late stage clinical evaluation in metastatic breast cancer NCT03262935), and the FDA accepted Byondis' Biologics License Application for the use of SYD985 in patients with HER2-positive unresectable locally advanced or metastatic breast cancer in mid-2022.