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.

AZD6738（通用名：塞拉塞替布，ceralasertib）是一款口服给药的选择性强效共济失调毛细血管扩张症和Rad3相关（Ataxia Telangiectasia and Rad3 Related，ATR）激酶抑制剂。本研究报告了一项II期临床试验：在以28天为一个周期的治疗方案中，给予该ATR丝氨酸/苏氨酸蛋白激酶口服抑制剂塞拉塞替布240mg，每日两次，于每个周期的第15~28天给药，联合度伐利尤单抗（durvalumab）1500mg，每4周的第1天给药，用于治疗晚期胃癌患者。入组的31例患者中，11例达到疾病稳定，13例出现疾病进展；客观缓解率（ORR）为22.6%，疾病控制率（DCR）为58.1%，中位无进展生存期（PFS）为3.0个月（95%置信区间[CI]：2.1~3.9），中位总生存期（OS）为6.7个月（95%CI：3.8~9.6）。ATM蛋白缺失或同源重组缺陷富集突变特征与更优的无进展生存期显著相关。多数常见不良事件均具有良好耐受性。塞拉塞替布联合度伐利尤单抗在经治转移性胃癌患者中展现出了具有前景的抗肿瘤活性及持久的临床缓解效果。