Drug intelligence / Profile preview

gilteritinib + venetoclax + azacitidine + cytarabine

Development stage
Phase 2
Lead developer
Astellas Pharma Global Development, Inc.
Modality
Small Molecules
Administration
Oral, Intravenous, Subcutaneous
01

Overview

This combination regimen, evaluated in the GANCE trial by the First Affiliated Hospital of Zhejiang University, is a multi-phase treatment strategy for newly diagnosed, intermediate-risk acute myeloid leukemia (AML) patients with FLT3-ITD mutations. The regimen consists of an induction phase using 'GVA' (gilteritinib, venetoclax, and azacitidine) followed by a consolidation phase using high-dose cytarabine (HiDAC) and gilteritinib, and a final maintenance phase with gilteritinib. Gilteritinib is a potent FLT3 inhibitor, venetoclax is a BCL-2 inhibitor that promotes apoptosis, azacitidine is a hypomethylating agent, and cytarabine is a pyrimidine analog that interferes with DNA synthesis. This approach aims to achieve deep molecular remission and potentially replace the need for allogeneic hematopoietic stem cell transplantation in fit patients. Note: The term 'HDAC' in the trial context refers to High-Dose Ara-C (cytarabine), rather than a histone deacetylase inhibitor.

Other names
GVA + HiDACGVA + HDAC ConsolidationGilteritinib + VA RegimenGVA + histone deacetylase inhibitor + gilteritinib
02

Targets

AXL (AXL receptor tyrosine kinase)BCL-2 (BCL-2 family)DNADNMT (DNA methyltransferase)FLT3 (Fms related receptor tyrosine kinase 3)DNA polymerase family

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