派安普利单抗，一种抗 PD-1 IgG1 抗体，用于治疗晚期或转移性上消化道癌。
Penpulimab, an anti-PD1 IgG1 antibody in the treatment of advanced or metastatic upper gastrointestinal cancers.
机构信息
Department of Medical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Adelaide Cancer Centre, Kurralta Park, Australia.
出版信息
Cancer Immunol Immunother. 2022 Oct;71(10):2371-2379. doi: 10.1007/s00262-022-03160-1. Epub 2022 Feb 15.
BACKGROUND
The safety and anti-tumor activity of penpulimab in patients with advanced upper gastrointestinal (UGI) cancers were evaluated in this study.
METHODS
Patients with advanced UGI cancers naive to immune checkpoint inhibitors were enrolled in two trials of penpulimab. In the Phase Ia/Ib trial in Australia, patients received penpulimab intravenous infusion of 1, 3 and 10 mg/kg every 2 weeks in dose-escalation phase and 200 mg every 2 weeks in dose-expansion phase. In the phase Ib/II trial conducted in China, patients received 200 mg penpulimab every 2 weeks. Primary endpoints were safety and tolerability for the phase Ia/Ib trial and the objective response rate for the phase Ib/II trial. The safety and efficacy of penpulimab in patients with UGI cancers in these two trials were evaluated.
RESULTS
A total of 67 patients with UGI cancers from Australia and China were enrolled in these two trials and had received penpulimab with a median of 6 (1-64) doses. 44.8% of patients experienced at least one treatment-related adverse event (TRAE), and 7.5% of patients experienced a grade ≥3 TRAE. Among 60 patients evaluable for response, the confirmed objective response rates ranged between 11.1 and 26.3% across cohorts for pancreatic cancer, cholangiocarcinoma, gastric or Gastroesophageal junction carcinoma (Gastric/GEJ), and hepatocellular carcinoma. 11/13 (85.0%) responders had ongoing responses at data cutoff date.
CONCLUSIONS
Penpulimab monotherapy demonstrated an acceptable safety and encouraged anti-tumor activity in patients with advanced UGI cancers. Further exploration in a large cohort of patients is warranted.
TRIAL REGISTRATION
Phase Ia/Ib trial in Australia (NCT03352531) and phase Ib/II trial in China (NCT04172506).
背景
本研究评估了 penpulimab 治疗晚期上消化道（UGI）癌症患者的安全性和抗肿瘤活性。
方法
本研究纳入了两批接受 penpulimab 治疗的晚期 UGI 癌症患者。在澳大利亚进行的 Ia/Ib 期临床试验中，患者接受 penpulimab 静脉输注，剂量递增阶段为 1、3 和 10 mg/kg，每 2 周一次，剂量扩展阶段为 200 mg，每 2 周一次。在中国进行的 Ib/II 期临床试验中，患者接受 200 mg penpulimab，每 2 周一次。Ia/Ib 期试验的主要终点为安全性和耐受性，Ib/II 期试验的主要终点为客观缓解率。评估了这两项试验中 penpulimab 治疗 UGI 癌症患者的安全性和有效性。
结果
共有来自澳大利亚和中国的 67 名 UGI 癌症患者入组这两项试验，中位接受了 6（1-64）个剂量的 penpulimab。44.8%的患者发生至少一次治疗相关不良事件（TRAEs），7.5%的患者发生≥3 级 TRAEs。在可评估疗效的 60 名患者中，胰腺癌、胆管癌、胃癌或胃食管交界处癌（胃/GEJ）和肝细胞癌的确认客观缓解率分别为 11.1%-26.3%。13 名应答者中有 11 名（85.0%）在数据截止日期时仍有持续应答。
结论
penpulimab 单药治疗晚期 UGI 癌症患者具有可接受的安全性和抗肿瘤活性。需要进一步在更大的患者队列中进行探索。
临床试验注册
澳大利亚的 Ia/Ib 期试验（NCT03352531）和中国的 Ib/II 期试验（NCT04172506）。
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