Abstract：
BACKGROUND: Cluster of differentiation (CD) 73-targeted immunotherapy and CD73 inhibition may reduce adenosine production, which can augment the host and/or immunotherapy response to tumours. We aimed to assess the safety and tolerability, pharmacokinetics, and antitumour activity of oleclumab, an anti-CD73 monoclonal antibody, in adult Japanese patients with advanced solid malignancies resistant to standard therapy.
METHODS: In this phase I, single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) or 3000 mg (Cohort 2) intravenously every 2 weeks.
RESULTS: In total, six patients were enrolled in the study (three in each cohort), and all six patients received the study treatment. The median patient age was 56.0 years and 4/6 were males. All patients (100%) reported adverse events (AEs) during the study; five (83.3%) patients reported AEs related to the study treatment. One (16.7%) patient reported a Grade 3 AE (neutrophil count decreased) that was not related to the study treatment. No AEs with an outcome of death were reported, and no patients reported AEs or serious AEs leading to oleclumab discontinuation/dose interruption. No dose-limiting toxicities were reported, and no patient discontinued due to an AE related to the study treatment. Oleclumab exposure increased dose proportionally. No patient achieved disease control at 8 weeks, and all six patients developed progressive disease.
CONCLUSIONS: Oleclumab was well tolerated in adult Japanese patients with advanced solid malignancies and no unexpected safety concerns were raised; oleclumab exposure increased with dose. Future studies on combination therapy with other agents are warranted.
METHODS: In this phase I, single-centre, open-label study, patients received oleclumab 1500 mg (Cohort 1) or 3000 mg (Cohort 2) intravenously every 2 weeks.
RESULTS: In total, six patients were enrolled in the study (three in each cohort), and all six patients received the study treatment. The median patient age was 56.0 years and 4/6 were males. All patients (100%) reported adverse events (AEs) during the study; five (83.3%) patients reported AEs related to the study treatment. One (16.7%) patient reported a Grade 3 AE (neutrophil count decreased) that was not related to the study treatment. No AEs with an outcome of death were reported, and no patients reported AEs or serious AEs leading to oleclumab discontinuation/dose interruption. No dose-limiting toxicities were reported, and no patient discontinued due to an AE related to the study treatment. Oleclumab exposure increased dose proportionally. No patient achieved disease control at 8 weeks, and all six patients developed progressive disease.
CONCLUSIONS: Oleclumab was well tolerated in adult Japanese patients with advanced solid malignancies and no unexpected safety concerns were raised; oleclumab exposure increased with dose. Future studies on combination therapy with other agents are warranted.
摘要：
背景：分化簇（CD）73靶向免疫疗法和CD73抑制可能会减少腺苷的产生，这可以增强宿主和/或免疫疗法对肿瘤的反应。我们旨在评估安全性和耐受性，药代动力学，和奥勒单抗的抗肿瘤活性，抗CD73单克隆抗体,在对标准治疗耐药的日本成年晚期实体恶性肿瘤患者中。
方法：在第一阶段，单中心,开放标签研究，患者每2周静脉内接受一次olelumab1500mg(队列1)或3000mg(队列2).
结果：总计，6名患者被纳入研究(每个队列3名)，所有6名患者都接受了研究治疗。患者年龄中位数为56.0岁，4/6为男性。所有患者(100%)在研究期间报告不良事件(AE);5名(83.3%)患者报告与研究治疗相关的AE。一名(16.7%)患者报告了与研究治疗无关的3级AE(中性粒细胞计数降低)。没有报告以死亡为结果的不良事件，并且没有患者报告AE或严重AE导致Olumumab停药/剂量中断。没有剂量限制性毒性报告，并且没有患者由于与研究治疗相关的AE而中断。Oleclumab暴露成比例增加剂量。没有患者在8周时实现疾病控制，所有六名患者都发展为进行性疾病。
结论：Oleclumab在患有晚期实体恶性肿瘤的日本成年患者中具有良好的耐受性，并且没有引起意外的安全性问题；随着剂量的增加，Oleclumab暴露增加。与其他药物联合治疗的未来研究是有必要的。
方法：在第一阶段，单中心,开放标签研究，患者每2周静脉内接受一次olelumab1500mg(队列1)或3000mg(队列2).
结果：总计，6名患者被纳入研究(每个队列3名)，所有6名患者都接受了研究治疗。患者年龄中位数为56.0岁，4/6为男性。所有患者(100%)在研究期间报告不良事件(AE);5名(83.3%)患者报告与研究治疗相关的AE。一名(16.7%)患者报告了与研究治疗无关的3级AE(中性粒细胞计数降低)。没有报告以死亡为结果的不良事件，并且没有患者报告AE或严重AE导致Olumumab停药/剂量中断。没有剂量限制性毒性报告，并且没有患者由于与研究治疗相关的AE而中断。Oleclumab暴露成比例增加剂量。没有患者在8周时实现疾病控制，所有六名患者都发展为进行性疾病。
结论：Oleclumab在患有晚期实体恶性肿瘤的日本成年患者中具有良好的耐受性，并且没有引起意外的安全性问题；随着剂量的增加，Oleclumab暴露增加。与其他药物联合治疗的未来研究是有必要的。
