Drug intelligence / Profile preview

decitabine + gemtuzumab ozogamicin

Development stage
Unknown
Lead developer
Eisai
Modality
Small Molecules, Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Monoclonal Antibodies → Antibody-Based Therapeutics
Administration
Intravenous
01

Overview

A two-drug oncology regimen that combines the hypomethylating agent decitabine with the CD33-directed antibody-drug conjugate gemtuzumab ozogamicin for treatment of acute myeloid leukemia and related myeloid neoplasms. Decitabine inhibits DNA methyltransferase, leading to DNA hypomethylation and chromatin opening, which can increase leukemia cell susceptibility to targeted cytotoxic agents. Gemtuzumab ozogamicin is an anti-CD33 monoclonal antibody conjugated to the cytotoxic payload calicheamicin; after CD33 binding and internalization, the linker is cleaved in lysosomes to release calicheamicin, causing DNA double-strand breaks and cell death. Sequential administration with decitabine has been investigated to enhance GO activity, with clinical studies reporting complete remissions in relapsed/refractory AML and improved response rates in older or unfit, newly diagnosed AML, though without overall survival benefit versus historical controls. Typical study dosing has used decitabine 20 mg/m2 daily for 5 days followed by GO 3 mg/m2 on day 5 or in fractionated doses on days 6, 9, and 12. Developers/manufacturers for the components are those of the individual agents rather than a uniquely branded combination.

Other names
decitabine plus gemtuzumab ozogamicindecitabine and gemtuzumab ozogamicinDAC + GO
02

Targets

DNMT1 (DNA (cytosine-5)-methyltransferase 1)DNACD33 (Myeloid cell surface antigen CD33)

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