Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study

BMC Cancer

Research

Zhengyun Zou¹  Zhiguo Luo²  Yu Chen³  Chuanliang Cui⁴  Lu Si⁴  Xuan Wang⁴  Zhihong Chi⁴  Jun Guo⁴  Xinan Sheng⁴  Qing Xu⁵  Taiyang Ma⁶  Qian Tan⁶  Yiwei Dou⁶  Renbing Jiang⁷  Jianfu Zhao⁸  Qingxia Fan⁹  Di Wu^1,10  Zhen Guo^1,10  Yu Jiang^1,11  Hongming Pan^1,12 

[1] Drum Tower Hospital, Affiliated to Medical School of Nanjing University, Nanjing, China;Fudan University Shanghai Cancer Center, Shanghai, China;Fujian Cancer Hospital, Fuzhou, China;Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China;Shanghai Tenth People’s Hospital, Shanghai, China;Taizhou Hanzhong Biomedical Co., Ltd. (A Member of Lepu Biopharma Co., Ltd.), Taizhou, China;The Affiliated Cancer Hospital of Xinjiang Medical University, Ürümqi, China;The First Affiliated Hospital of Jinan University, Guangzhou, China;The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;The First Hospital of Jilin University, Changchun, China;West China Hospital, Sichuan University, Chengdu, China;Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, China;

关键词: PD-1;    Monoclonal antibody;    Pucotenlimab;    HX008;    Melanoma;   

DOI  :  10.1186/s12885-022-10473-y

 received in 2022-07-20, accepted in 2022-12-21,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundPucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2.MethodsIn this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity.ResultsOne-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator’s assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037–4.074) months and 2.46 (95% CI, 2.004–4.008) months based on IRC and investigator’s assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963–26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure.ConclusionsPucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma.Trial registrationClinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).

【 授权许可】

CC BY   
© The Author(s) 2023

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