Nucleus Network, Melbourne, Victoria, Australia.
Department of Medicine, University of Melbourne, Heidelberg, Victoria, Australia.
Drug Des Devel Ther. 2020 Mar 18;14:1177-1189. doi: 10.2147/DDDT.S243787. eCollection 2020.
Camrelizumab inhibits PD-1 in non-clinical models and showed typical non-clinical pharmacokinetic (PK) and safety profiles for an IgG4 monoclonal antibody. We report results from the First-in-Human Phase 1 trial of camrelizumab in Australian population.
Camrelizumab was administered to patients with advanced solid tumors who had failed standard therapies. In the dose-escalation phase (n=23), camrelizumab was administered intravenously at 1 mg/kg, 3 mg/kg, 6 mg/kg, and 10 mg/kg every 2 weeks. In dose expansion (n=26), camrelizumab was given at 200 mg or 600 mg every 4 weeks.
Two dose-limiting toxicities were observed during dose escalation: transaminase elevation and diarrhea (both grade 3). Overall, treatment-related adverse events were consistent with the expected toxicity profile of immune checkpoint inhibition, with the striking exception of the dose-related development of angiomatous skin lesions characterized as reactive cutaneous capillary endothelial proliferation. The PK profile showed a dose-progressive increase in half-life from 3 days at 1 mg/kg to 7 days at 10 mg/kg. Moreover, receptor occupancy assays showed a PD-1 occupancy of >50% in most patients out to 28 days post-dose. The objective response rate was 15.2% (95% CI 6.3-28.9).
Camrelizumab has manageable toxicity and encouraging preliminary antitumor activity in advanced solid tumors in Australia.
ClinicalTrials.gov Identifier: NCT02492789.
卡瑞利珠单抗在非临床模型中抑制 PD-1，表现出典型的 IgG4 单克隆抗体的非临床药代动力学（PK）和安全性特征。我们报告了卡瑞利珠单抗在澳大利亚人群中的首次人体 I 期临床试验结果。
卡瑞利珠单抗用于标准治疗失败的晚期实体瘤患者。在剂量递增阶段（n=23），卡瑞利珠单抗每 2 周静脉注射 1 mg/kg、3 mg/kg、6 mg/kg 和 10 mg/kg。在剂量扩展阶段（n=26），卡瑞利珠单抗每 4 周给予 200 mg 或 600 mg。
在剂量递增阶段观察到 2 例剂量限制性毒性：转氨酶升高和腹泻（均为 3 级）。总体而言，治疗相关不良事件与免疫检查点抑制的预期毒性特征一致，唯一显著的例外是与剂量相关的血管性皮肤病变的发展，表现为反应性皮肤毛细血管内皮增生。PK 特征显示半衰期从 1 mg/kg 时的 3 天逐渐增加到 10 mg/kg 时的 7 天。此外，受体占有率测定显示，大多数患者在给药后 28 天 PD-1 占有率>50%。客观缓解率为 15.2%（95%CI 6.3-28.9）。
卡瑞利珠单抗在澳大利亚晚期实体瘤患者中具有可管理的毒性和令人鼓舞的初步抗肿瘤活性。
ClinicalTrials.gov 标识符：NCT02492789。
