The Cancer Therapy Evaluation Program (CTEP) is accepting Letters of Intent (LOIs) to conduct clinical studies using AZD6738, an ataxia telangiectasia and Rad3 related (ATR) inhibitor, which is being developed by CTEP as an anticancer agent in collaboration with AstraZeneca. CTEP will also consider requests to supply AZD6738 for nonclinical studies. All clinical and nonclinical researchers possessing an interest in working with the agent are welcome to apply. Proposals for clinical trials should be supported by a strong rationale and robust preclinical data (see “Components of a Competitive Letter of Intent" at: http://ctep.cancer.gov/protocolDevelopment/lois_concepts.htm).
AZD6738 (Ceralasertib) is a potent and selective orally bioavailable kinase inhibitor of ATR (Guichard et al., 2013). It inhibits the phosphorylation of direct downstream substrate CHK1 while increasing the phosphorylation of ataxia telangiectasia mutated (ATM)-dependent substrate checkpoint kinase 2 (CHK2) and γH2AX. This is associated with impaired S-phase cell cycle progression with prolonged inhibition, causing replication fork stalling, collapse, and irreversible damage. AZD6738 is active as a single agent across cancer cell line panels but shows enhanced sensitivity in cell lines with ATM-pathway defects. AZD6738, when used in combination with DNA damage inducing agents gemcitabine, cisplatin, or ionizing radiation (IR), shows enhanced synergistic cell killing activity. AZD6738 potentiates the cytotoxicity of cisplatin and gemcitabine in non-small-cell lung cancer (NSCLC) cell lines with intact ATM kinase signaling, and potently synergizes with cisplatin in ATM-deficient NSCLC cells (Vendetti et al., 2015).
All proposals approved by CTEP will be sent to the industry collaborator for a commitment to supply drug for the study.
For more information and the LOI Submission Form please see related documents below.