Clinical Pipeline

Phase 1Phase 2Phase 3

ASTX660

Dual Antagonist Inhibition of Apoptosis Proteins (IAPs) XIAP and cIAP (Advanced Solid Tumors and Lymphomas)

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Ownership: Astex

Mechanism of Action: Dual Antagonist of Inhibitors of Apoptosis Proteins (IAPs) XIAP and cIAP

Indication: Advanced Solid Tumors and Lymphomas

How this therapy can help

Apoptosis or programmed cell death, while part of normal cell behavior, is often altered in cancer cells and can be prevented by overexpression of anti-apoptotic proteins, such as XIAP and cIAP. These IAPs are key regulators of anti-apoptotic and pro-survival signaling pathways and their dysregulation, through overexpression or loss of endogenous antagonists, occurs in various cancers. This is associated with tumor growth, poor prognosis and resistance to treatment, making IAPs attractive targets for anticancer therapy. ASTX660 has a unique IAP antagonist molecular profile, with balanced XIAP and cIAP antagonist activity. Given the importance of XIAP in regulating both extrinsic and intrinsic apoptosis pathways, improved XIAP antagonism, as demonstrated with ASTX660 compared to other IAP antagonists in the clinic, has the potential to result in enhanced pro-apoptotic activity and tumor cell death.

Clinical status

ASTX660 is currently being evaluated in patients with peripheral T-cell lymphoma (PTCL) and cutaneous T-cell lymphoma as part of the Phase 2 portion of a Phase 1/2 study in patients with advanced solid tumors and lymphomas to determine safety, pharmacokinetics and preliminary activity

ASTX660 is also being studied in combination with oral decitabine and cedazuridine in the treatment of acute myeloid leukemia (AML).

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