Pucotenlimab（HX008）-一种人源化 IgG4 单克隆抗体治疗局部晚期或转移性黑色素瘤患者的安全性和有效性：一项单臂、多中心、II 期研究。
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.
机构信息
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.
Fujian Cancer Hospital, Fuzhou, China.
出版信息
BMC Cancer. 2023 Feb 6;23(1):121. doi: 10.1186/s12885-022-10473-y.
BACKGROUND
Pucotenlimab 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.
METHODS
In 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.
RESULTS
One-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 30, 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.
CONCLUSIONS
Pucotenlimab as a ≥ 2 line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma.
TRIAL REGISTRATION
Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).
背景
Pucotenlimab 是一种新型的重组人源化抗 PD-1（程序性死亡受体-1）单克隆抗体，属于 IgG4/κ亚型，可选择性阻断 PD-1 与其配体 PD-L1 和 PD-L2 的结合。
方法
本 2 期临床试验纳入了局部晚期或转移性黑色素瘤患者，这些患者经常规治疗（化疗、靶向治疗、干扰素、IL-2 等）失败。患者每 3 周接受 3mg/kg 的 Pucotenlimab 治疗，直至疾病进展、无法耐受毒性或因任何其他原因停止治疗。主要终点为总缓解率（ORR）。次要终点包括疾病控制率（DCR）、缓解持续时间（DOR）、无进展生存期（PFS）、总生存期（OS）和毒性。
结果
截至 2021 年 7 月 30 日，共有 119 例患者入组并随访 19.32 个月（范围为 15.901-24.608 个月）。基于独立评估委员会（IRC）和研究者根据 RECIST v1.1 评估的结果，ORR 分别为 20.17%（24/119，95%CI，13.370%-28.506%）和 20.31%（24/119）。IRC 和研究者根据 RECIST v1.1 评估的 PFS 中位数分别为 2.89（95%CI，2.037-4.074）个月和 2.46（95%CI，2.004-4.008）个月。OS 中位数为 16.59（95%CI，13.963-26.973）个月。77.3%（119/159）的患者发生了治疗相关不良事件（TRAEs）。3 级及以上 TRAEs 的发生率为 15.1%（18/119）。此外，无 TRAEs 导致患者死亡。生物标志物分析显示，嗜酸性粒细胞趋化因子（CCL11）和单核细胞趋化蛋白-1（CCL2）与治疗反应相关，而 TNF-α 和 VEGF 与治疗失败相关。
结论
Pucotenlimab 作为二线以上治疗药物，对局部晚期或转移性黑色素瘤患者具有良好的疗效和可耐受的毒性。
试验注册
Clinicaltrials.gov 标识符：NCT04749485（于 2021 年 11 月 2 日回顾性注册）。
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