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vorinostat + gemtuzumab ozogamicin
- Development stage
- Phase 2
- Lead developer
- Fred Hutchinson Cancer Research Institute
- Modality
- Cytotoxic ADCs → Antibody-Drug Conjugates (ADCs) → Antibody Conjugates → Antibody-Based Therapeutics, Small Molecules
- Administration
- Oral, Intravenous
01
Overview
Vorinostat + gemtuzumab ozogamicin is a combination therapy investigated for the treatment of acute myeloid leukemia (AML), particularly in older adults. Vorinostat (Zolinza) is a small molecule histone deacetylase (HDAC) inhibitor that targets Class I and Class II HDACs, leading to increased histone acetylation and the modulation of gene expression, which can sensitize cancer cells to chemotherapy. Gemtuzumab ozogamicin (Mylotarg) is an antibody-drug conjugate (ADC) consisting of a monoclonal antibody directed against CD33, a cell surface antigen frequently expressed on AML blasts, linked to a cytotoxic calicheamicin derivative. Upon binding to CD33 and internalization, the calicheamicin payload is released, causing double-strand DNA breaks and cell death. This combination was evaluated by the Fred Hutchinson Cancer Center in a Phase II clinical trial (NCT00673153) as induction, consolidation, and maintenance therapy for patients aged 60 and older with previously untreated non-M3 AML, based on preclinical evidence of synergistic activity.
- Other names
- suberoylanilide hydroxamic acid
02
Targets
CD33 (Myeloid cell surface antigen CD33)HDAC1 (Histone Deacetylase 1)HDAC2 (Histone deacetylase 2)HDAC3 (Histone Deacetylase 3)HDAC6 (Histone deacetylase 6)
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