Phase II study of ceralasertib (AZD6738) in combination with durvalumab in patients with advanced gastric cancer.

• DOI: 10.1200/jco.2022.40.16_suppl.4045
• Publication Date: 2022-06-06T16:16:56Z
• Authors: Minsuk Kwon; Seung Tae Kim; Jung Yong Hong; Gahyun Kim; Simon Smith; Peter G. Mortimer; Bienvenu LoembE; Emma Dean; Won Ki Kang; Jeeyun Lee
• Keywords: Durvalumab; Dysgeusia; Clinical endpoint

4045 Background: Alterations in DNA damage response (DDR) and repair are associated with genomic instability increased somatic tumor mutational burden, modulating using specific inhibitors is a promising strategy to boost the efficacy of cancer immunotherapy. Ceralasertib an oral inhibitor serine/threonine protein kinase Ataxia Telangiectasia Rad3 Related (ATR), which crucial cell’s replication stress. Methods: This phase 2 trial was designed evaluate safety ceralasertib combination durvalumab patients advanced gastric (AGC). The study drug regimen 240 mg BD days 15 28 28-day cycle at 1500 day 1 every 4 weeks. primary end point overall rate (ORR) by RECIST (v1.1). Exploratory biomarker analysis performed fresh biopsies all enrolled patients. Results: 31 (median no. prior lines, 2; range, 2-5) were between Jul 2019 Mar 2020. All had confirmed microsatellite stable tumors, 5 EBV positive, 24 PD-L1 positive (CPS≥1). Two received anti-PD-1 treatment. At time data cut-off (Dec 2020), 30 evaluable for response: 7 partial responses (one patient treatment), 11 disease, 12 disease progression observed. ORR 22.6%, DCR 58.1 %, median PFS 3.0 months (95% confidence interval (CI), 2.1-3.9), duration 5.7 CI, 4.9-6.5), OS 6.7 3.8-9.6). A subgroup (n = 11) who loss ATM expression and/or high proportion signature attributable homologous deficiency (sig. HRD) demonstrated significantly longer than those 12) intact low sig. HRD (5.60 vs 1.65 months, hazard ratio 0.13, 95% CI 0.045-0.39, long-rank P < 0.001). most common adverse events any grade fatigue 22, 71.0%), nausea 20, 64.5%) anorexia 19, 61.3%), 3 or more anemia thrombocytopenia 11, 35.5% each). Conclusions: anti-tumor activity durable refractory AGC. Clinical information: NCT03780608.