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Abstract：
BACKGROUND: Ezabenlimab (BI 754091) is a humanised monoclonal antibody targeting programmed cell death protein-1. We report results from open-label, dose-escalation/expansion, Phase I trials that evaluated the safety, maximum tolerated dose (MTD), pharmacokinetics and antitumour activity of ezabenlimab at the recommended Phase II dose in patients with selected advanced solid tumours.
METHODS: Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States. Study 1381.4 (NCT03433898) was conducted in Japan. Study 1381.3 (NCT03780725) was conducted in the Netherlands. The primary endpoints were: number of patients experiencing dose-limiting toxicities (DLTs) in the first cycle (dose escalation parts), number of patients with DLTs during the entire treatment period and objective response (dose expansion part of Study 1381.1).
RESULTS: Overall, 117 patients received ezabenlimab intravenously every 3 weeks (80 mg, n = 3; 240 mg, n = 111; 400 mg, n = 3). No DLTs were observed and the MTD was not reached. Fifty-eight patients (52.3%) had grade ≥ 3 adverse events, most commonly anaemia (10.8%) and fatigue (2.7%). In 111 assessed patients treated with ezabenlimab 240 mg, disease control rate was 56.8% and objective response rate was 16.2%. Three patients had complete response; at data cut-off (November 2021) one remained in response and was still receiving ongoing treatment (duration of response [DoR]: 906 days). Partial responses occurred across several tumour types; DoR ranged from 67 to 757 days.
CONCLUSIONS: Ezabenlimab was well tolerated and associated with durable antitumour activity in multiple solid tumours, comparable to other immune checkpoint inhibitors in similar patient populations and treatment settings.
METHODS: Study 1381.1 (NCT02952248) was conducted in Canada, the United Kingdom and the United States. Study 1381.4 (NCT03433898) was conducted in Japan. Study 1381.3 (NCT03780725) was conducted in the Netherlands. The primary endpoints were: number of patients experiencing dose-limiting toxicities (DLTs) in the first cycle (dose escalation parts), number of patients with DLTs during the entire treatment period and objective response (dose expansion part of Study 1381.1).
RESULTS: Overall, 117 patients received ezabenlimab intravenously every 3 weeks (80 mg, n = 3; 240 mg, n = 111; 400 mg, n = 3). No DLTs were observed and the MTD was not reached. Fifty-eight patients (52.3%) had grade ≥ 3 adverse events, most commonly anaemia (10.8%) and fatigue (2.7%). In 111 assessed patients treated with ezabenlimab 240 mg, disease control rate was 56.8% and objective response rate was 16.2%. Three patients had complete response; at data cut-off (November 2021) one remained in response and was still receiving ongoing treatment (duration of response [DoR]: 906 days). Partial responses occurred across several tumour types; DoR ranged from 67 to 757 days.
CONCLUSIONS: Ezabenlimab was well tolerated and associated with durable antitumour activity in multiple solid tumours, comparable to other immune checkpoint inhibitors in similar patient populations and treatment settings.
摘要：
背景：Ezabenlimab（BI754091）是一种靶向程序性细胞死亡蛋白-1的人源化单克隆抗体。我们报告了开放标签的结果，剂量递增/扩张，评估安全性的第一阶段试验，最大耐受剂量（MTD），推荐II期剂量的Ezabenlimab在某些晚期实体瘤患者中的药代动力学和抗肿瘤活性。
方法：研究1381.1（NCT02952248）在加拿大进行，英国和美国。研究1381.4(NCT03433898)在日本进行。研究1381.3(NCT03780725)在荷兰进行。主要终点是：在第一个周期（剂量递增部分）中经历剂量限制性毒性（DLT）的患者人数，在整个治疗期间患有DLT的患者数量和客观反应（研究1381.1的剂量扩展部分）。
结果：总体而言，117例患者每3周静脉注射ezabenlimab（80mg，n=3；240毫克，n=111；400毫克，n=3)。没有观察到DLT并且没有达到MTD。58例患者（52.3%）有≥3级不良事件，最常见的是贫血(10.8%)和疲劳(2.7%)。在111名评估的患者中，接受了240毫克的Ezabenlimab治疗，疾病控制率为56.8%,客观缓解率为16.2%。三名患者完全缓解；在数据截止日期（2021年11月），一名患者仍处于缓解状态，仍在接受持续治疗（缓解持续时间[DoR]：906天）。在几种肿瘤类型中发生部分反应;DoR范围为67至757天。
结论：Ezabenlimab在多种实体瘤中具有良好的耐受性和持久的抗肿瘤活性。在相似的患者群体和治疗环境中,与其他免疫检查点抑制剂相当.
方法：研究1381.1（NCT02952248）在加拿大进行，英国和美国。研究1381.4(NCT03433898)在日本进行。研究1381.3(NCT03780725)在荷兰进行。主要终点是：在第一个周期（剂量递增部分）中经历剂量限制性毒性（DLT）的患者人数，在整个治疗期间患有DLT的患者数量和客观反应（研究1381.1的剂量扩展部分）。
结果：总体而言，117例患者每3周静脉注射ezabenlimab（80mg，n=3；240毫克，n=111；400毫克，n=3)。没有观察到DLT并且没有达到MTD。58例患者（52.3%）有≥3级不良事件，最常见的是贫血(10.8%)和疲劳(2.7%)。在111名评估的患者中，接受了240毫克的Ezabenlimab治疗，疾病控制率为56.8%,客观缓解率为16.2%。三名患者完全缓解；在数据截止日期（2021年11月），一名患者仍处于缓解状态，仍在接受持续治疗（缓解持续时间[DoR]：906天）。在几种肿瘤类型中发生部分反应;DoR范围为67至757天。
结论：Ezabenlimab在多种实体瘤中具有良好的耐受性和持久的抗肿瘤活性。在相似的患者群体和治疗环境中,与其他免疫检查点抑制剂相当.
