Efficacy and Safety of Iparomlimab, an Anti-PD-1 Antibody, in Patients with Advanced Solid Tumors: A Phase 1c Study

IF 3.4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2024-09-14 DOI:10.1007/s12325-024-02981-z

Jianping Xiong, Weiwei Ouyang, Mengxiang Yang, Zhenyuan Gao, Huan Zhou, Hanmei Lou, Yabing Guo, Zhongyuan Xu, Ling Zheng, Ying Liu, Zhongfeng Wang, Ping Sun, Huerxidan Niyazi, Jianhua Wang, Yan Chen, Baihui Zhang, Lingyan Li, Xiaoyan Kang, Weijian Guo

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引用次数: 0

Abstract

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.

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抗 PD-1 抗体 Iparomlimab 对晚期实体瘤患者的疗效和安全性：1c期研究

简介伊帕单抗（QL1604）是一种针对程序性细胞死亡蛋白1（PD-1）的人源化免疫球蛋白G4 mAb。方法在这项开放标签的1c期研究中，入组了晚期或转移性实体瘤患者，这些患者要么治疗失败，要么没有标准疗法可用，他们接受了静脉注射伊帕单抗，剂量为3 mg/kg，每3周一次。主要疗效终点是研究者根据实体瘤反应评价标准（RECIST）1.1版评估的客观反应率（ORR）。结果2020年7月20日至2021年9月6日期间，71名患者入组并接受了至少一次伊帕单抗治疗。ORR为9.9%（7/71），疾病控制率为36.6%（26/71）。所有应答者的中位应答持续时间为10.7个月[95%置信区间（CI），1.4-无法估计]。此外，中位进展时间、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%）患者出现了治疗相关不良事件（TRAE）（≥3级，19.7%）。最常见的不良反应（≥10%）是贫血（18.3%）。共有 20 例（28.2%）出现免疫相关不良事件（≥ 3 级，7.0%）。导致停药的不良反应有4例（5.6%），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）。这些结果支持进一步研究iparomlimab在晚期实体瘤中作为单药或联合疗法的应用。追溯注册于 2023-03-24。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.