Drug intelligence / Profile preview

etrumadenant + IPI-549 + pegylated liposomal doxorubicin

Development stage
Phase 1
Lead developer
Gilead Sciences
Modality
Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules, Nanoparticles → Drug Delivery Systems
Administration
Oral, Intravenous
01

Overview

This drug is a **combination regimen** consisting of: - **etrumadenant**: an investigational, orally bioavailable, small molecule dual antagonist of the adenosine A2a and A2b receptors. Etrumadenant is designed to block adenosine-mediated immunosuppression in the tumor microenvironment, restoring antitumor immune cell activity by disrupting adenosine signaling on T, NK, and myeloid cells[5][3]. - **IPI-549 (eganelisib)**: a first-in-class, orally administered, highly selective PI3K-γ inhibitor. IPI-549 acts to reprogram macrophages from immunosuppressive to immunostimulatory, enhancing antitumor responses, particularly in combination with immunotherapeutics such as checkpoint inhibitors[2][8]. - **pegylated liposomal doxorubicin**: a formulation of the anthracycline chemotherapeutic doxorubicin encapsulated in pegylated liposomes for improved pharmacokinetics and reduced toxicity. Doxorubicin acts via DNA intercalation and inhibition of topoisomerase II, causing tumor cell apoptosis. This combination is designed to synergize immunomodulatory blockade (adenosine pathway and PI3K-γ pathways) with cytotoxic chemotherapy for enhanced antitumor efficacy. Main indication under investigation is for advanced and metastatic solid tumors, including metastatic colorectal cancer.

Brand names
Caelyx
Other names
eganelisibliposomal doxorubicinPLD
02

Targets

ADORA2A (Adenosine A₂A Receptor)ADORA2B (Adenosine A2B receptor)DNATOP2A (DNA topoisomerase II)PIK3CG (Phosphatidylinositol 4,5-bisphosphate 3-kinase gamma)

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