AstraZeneca's ATR Inhibitor Ceralasertib Granted IND Approval in China for Combination Therapy in Advanced Solid Tumors

The official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration disclosed that the ceralasertib film-coated tablet, submitted by AstraZeneca, has received tacit approval for clinical trials. The proposed indication is: combination treatment with the PD-L1 inhibitor durvalumab for patients with advanced solid tumors. Public information indicates that ceralasertib is an ATR inhibitor under research by AstraZeneca and is currently undergoing Phase 2 clinical studies worldwide.

Screenshot source: CDE official website

ATR Has Been Considered One of the Most Promising Synthetic Lethal Targets After PARPATR and ATM are two key proteins in the DNA damage response signaling network, activated by DNA damage. ATR inhibitors can disrupt DNA damage repair by blocking the ATR-mediated signaling pathway. Studies have shown that ATR inhibitors can induce a synthetic lethal effect in tumor cells with ATM deficiency, leading to the death of ATM-deficient tumor cells without affecting normal cells.

Ceralasertib (previously known as AZD6738) is an ATR inhibitor currently under research by AstraZeneca. According to the ClinicalTrials website, AstraZeneca is conducting clinical trials of this drug as a monotherapy or in combination with other therapies for various types of cancer, including ceralasertib as a monotherapy and in combination with durvalumab for the treatment of melanoma. Durvalumab is an anti-PD-L1 monoclonal antibody. Preclinical studies have shown that ATR inhibitors, both as a monotherapy and in combination with other drugs, have therapeutic potential for solid tumors and hematological malignancies.

Earlier, AstraZeneca announced the results of a Phase 2 clinical study on ceralasertib at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting. This Phase 2 clinical trial aimed to evaluate the efficacy and safety of ceralasertib combined with durvalumab in treating patients with metastatic melanoma who failed anti-PD-1 monoclonal antibody therapy. The primary endpoint was the overall response rate (ORR) assessed according to RECIST (v1.1). The results showed that among the 30 patients enrolled in the study, the ORR was 30.0%, including 9 cases of partial response (PR), 10 cases achieving stable disease (SD), and 10 cases with progressive disease (PD); the disease control rate (DCR) was 63.3%, the median progression-free survival (PFS) was 7.1 months, and the median overall survival (OS) was 14.2 months. The findings indicated that the combination of ceralasertib and durvalumab demonstrated promising anti-tumor activity, especially in melanoma patients for whom standard treatments, including anti-PD-1 monoclonal antibody therapy, had failed. The clinical research results were also published in the international oncology journal, Journal of Clinical Oncology (JCO).

References:

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Jun 7, 2022. From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2]Phase II study of ceralasertib (AZD6738), in combination with durvalumab in patients with metastatic melanoma who have failed prior anti-PD-1 therapy. Retrieved May 28，2021. From https://ascopubs.org/doi/abs/10.1200/JCO.2021.39.15_suppl.9514

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