AZD6738, in combination with durvalumab in advanced gastric cancer

AZD6738 is an orally dosed selective and potent inhibitor of Ataxia Telangiectasis and Rad3 Related (ATR) kinase. We report phase 2 trial , an oral inhibitor of the serine/threonine protein kinase Ataxia Telangiectasia and Rad3 Related (ATR), ceralasertib at 240 mg BD on days 15 to 28 in a 28-day cycle in combination with durvalumab at 1500 mg day 1 every 4 weeks in patients with advanced gastric cancer. Among enrolled 31 patients, 11 stable disease, and 13 disease progression were observed. The ORR was 22.6%, DCR 58.1 %, median PFS 3.0 months (95% confidence interval (CI), 2.1-3.9), and median OS was 6.7 months (95% CI, 3.8-9.6). ATM protein loss or enriched mutation signature of homologous repair deficiency were associated with superior PFS. Most common adverse events were tolerable. Ceralasertib in combination with durvalumab demonstrated promising anti-tumor activity with durable responses in pretreated metastatic gastric cancer patients.