Single-center phase 2 trial of ceralasertib in patients with ARID1A-deficient solid malignancies

ARID1A is frequently mutated in cancer. Motivated by the preclinical synthetic lethality between ARID1A loss and ATR inhibition, researchers at University of California San Francisco performed a phase 2 study of the ATR inhibitor ceralasertib in locally advanced or metastatic ARID1A-deficient solid tumors. Patients received ceralasertib 160 mg twice daily on days 1-14 every 28 days. Among 29 efficacy-evaluable patients, the confirmed objective response rate was 14%. All 4 responses, including 3 complete responses, occurred in endometrioid endometrial carcinoma or ovarian clear cell carcinoma, with an ORR of 33% and a median duration of response of 33.7 months in this subset. Including one patient with uterine carcinosarcoma who had stable disease, ORR was 31% among the 13 patients with gynecologic malignancies. The authors conclude that ceralasertib monotherapy demonstrated promising antitumor activity in ARID1A-deficient gynecologic malignancies.