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capivasertib + venetoclax + dexamethasone
- Development stage
- Unknown
- Lead developer
- AstraZeneca
- Modality
- Orthosteric Ligands → Classical Binding Small Molecules → Small Molecules
- Administration
- Oral, Intravenous
01
Overview
This combination therapy is an investigational regimen being evaluated in the HEM-iSMART (ITCC-104) master protocol, specifically Sub-Protocol E, for the treatment of relapsed or refractory acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in children and young adults. The regimen consists of capivasertib, a potent, selective pan-AKT inhibitor; venetoclax, a small-molecule BCL-2 inhibitor; and dexamethasone, a synthetic glucocorticoid. The rationale for this combination is to target the PI3K/AKT/mTOR (PAM) signaling pathway, which is frequently activated in relapsed ALL, while simultaneously inducing apoptosis via BCL-2 inhibition and enhancing glucocorticoid sensitivity. The trial, led by the Princess Maxima Center for Pediatric Oncology, stratifies patients based on the presence of PAM pathway alterations or the lack of mutations.
- Other names
- Capivasertib + Venetoclax + Dexamethasone
02
Targets
PKA (Cyclic amp-dependent protein kinase)GR (Glucocorticoid receptor)RPS6KB1 (Ribosomal protein S6 kinase beta-1)AKT2 (Rac-beta serine/threonine-protein kinase)AKT1 (Proto-oncogene serine/threonine-protein kinase Akt1)BCL2L1 (B-cell lymphoma-extra large protein)
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