依帕利单抗，一种 PD-1 抗体，治疗晚期实体瘤患者的疗效和安全性：一项 1c 期研究。
Efficacy and Safety of Iparomlimab, an Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors: A Phase 1c Study.
机构信息
Department of Medical Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China.
Phase I Ward, Guizhou Cancer Hospital, Guiyang, China.
出版信息
Adv Ther. 2024 Nov;41(11):4153-4171. doi: 10.1007/s12325-024-02981-z. Epub 2024 Sep 14.
INTRODUCTION
Iparomlimab (QL1604) is a humanized immunoglobulin G4 mAb against programmed cell death protein 1 (PD-1). Here, we report the preliminary efficacy, safety, pharmacokinetics, and immunogenicity of iparomlimab in patients with advanced solid tumors.
METHODS
In this open-label, phase 1c study, patients with advanced or metastatic solid tumors, either failed or had no standard therapies available, were enrolled and received intravenous iparomlimab at 3 mg/kg once every 3 weeks. The primary efficacy endpoint was the objective response rate (ORR) assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
RESULTS
Between July 20, 2020, and September 6, 2021, 71 patients were enrolled and received at least one dose of iparomlimab. The ORR was 9.9% (7/71) and disease control rate was 36.6% (26/71). Median duration of response of all responders was 10.7 months [95% confidence interval (CI), 1.4-not estimable]. Additionally, the median time to progression, progression-free survival, and overall survival were 1.4 months (95% CI, 1.4-2.8), 1.4 months (95% CI, 1.4-2.7), and 9.7 months (95% CI, 7.2-15.3), respectively. A total of 52 (73.2%) patients experienced treatment-related adverse events (TRAEs) (grade ≥ 3, 19.7%). The most common TRAE (≥ 10%) was anemia (18.3%). A total of 20 (28.2%) experienced immune-related adverse events (grade ≥ 3, 7.0%). TRAEs leading to discontinuation of study drug occurred in 4 (5.6%) patients, including immune-mediated myocarditis (2 patients), Guillain-Barré syndrome (1 patient), and diarrhea (1 patient).
CONCLUSIONS
Iparomlimab showed preliminary clinical activity and had a manageable safety profile in patients with advanced solid tumors. These results support further investigation of iparomlimab as monotherapy or in combination therapy in advanced solid tumors.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT05801094. Retrospectively registered in 2023-03-24.
简介
Iparomlimab（QL1604）是一种针对程序性死亡蛋白 1（PD-1）的人源化 IgG4 mAb。在此，我们报告了晚期实体瘤患者中 iparomlimab 的初步疗效、安全性、药代动力学和免疫原性。
方法
在这项开放标签、1c 期研究中，纳入了晚期或转移性实体瘤患者，这些患者要么已经失败，要么没有标准治疗方法，他们接受了静脉注射 iparomlimab，剂量为 3mg/kg，每 3 周一次。主要疗效终点是根据实体瘤反应评估标准（RECIST）1.1 版，由研究者评估的客观缓解率（ORR）。
结果
2020 年 7 月 20 日至 2021 年 9 月 6 日，共 71 名患者入组并接受了至少一剂 iparomlimab 治疗。ORR 为 9.9%（7/71），疾病控制率为 36.6%（26/71）。所有应答者的中位缓解持续时间为 10.7 个月[95%置信区间（CI），1.4-不可估计]。此外，中位无进展生存期、无进展生存期和总生存期分别为 1.4 个月（95%CI，1.4-2.8）、1.4 个月（95%CI，1.4-2.7）和 9.7 个月（95%CI，7.2-15.3）。共有 52 名（73.2%）患者发生了与治疗相关的不良事件（TRAEs）（≥3 级，19.7%）。最常见的 TRAE（≥10%）是贫血（18.3%）。共有 20 名（28.2%）患者发生了免疫相关的不良事件（≥3 级，7.0%）。有 4 名（5.6%）患者因 TRAE 而停止了研究药物的使用，包括免疫介导的心肌炎（2 例）、格林-巴利综合征（1 例）和腹泻（1 例）。
结论
Iparomlimab 对晚期实体瘤患者表现出初步的临床疗效，安全性可控。这些结果支持进一步研究 iparomlimab 作为单药或联合治疗在晚期实体瘤中的应用。
临床试验注册
ClinicalTrials.gov 标识符，NCT05801094。2023 年 3 月 24 日回顾性注册。
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