Vadastuximab talirine (SGN-CD33A)

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General information

Class/mechanism from the NCI Drug Dictionary: An immunoconjugate consisting of a humanized monoclonal antibody that is engineered to contain cysteine residues that are conjugated to the synthetic, DNA cross-linking, pyrrolobenzodiazepine dimer SGD-1882, via the protease-cleavable linker maleimidocaproyl-valine-alanine dipeptide, with potential antineoplastic activity. The monoclonal antibody portion of the vadastuximab talirine specifically binds to the cell surface antigen CD33. This causes the internalization of vadastuximab talirine, and the release of the cytotoxic moiety SGD-1882. SGD-1882 binds to and crosslinks DNA, which results in both cell cycle arrest and the induction of apoptosis in CD33-expressing tumor cells. CD33, a transmembrane receptor, is expressed on myeloid leukemia cells.
Route: IV
Extravasation: no information

For conciseness and simplicity, currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.

Preliminary data

Acute myeloid leukemia

  • Phase 1: Stein EM, Walter RB, Erba HP, Fathi AT, Advani AS, Lancet JE, Ravandi F, Kovacsovics T, DeAngelo DJ, Bixby D, Faderl S, Jillella AP, Ho PA, O'Meara MM, Zhao B, Biddle-Snead C, Stein AS. A phase 1 trial of vadastuximab talirine as monotherapy in patients with CD33-positive acute myeloid leukemia. Blood. 2018 Jan 25;131(4):387-396. Epub 2017 Dec 1. link to original article link to PMC article PubMed NCT01902329
  • Phase 1: Fathi AT, Erba HP, Lancet JE, Stein EM, Ravandi F, Faderl S, Walter RB, Advani AS, DeAngelo DJ, Kovacsovics TJ, Jillella A, Bixby D, Levy MY, O'Meara MM, Ho PA, Voellinger J, Stein AS. A phase 1 trial of vadastuximab talirine combined with hypomethylating agents in patients with CD33-positive AML. Blood. 2018 Sep 13;132(11):1125-1133. Epub 2018 Jul 25. link to original article link to PMC article PubMed NCT01902329

Also known as

  • Code name: 33A, SGN-CD33A