STING 激动剂 MIW815（ADU-S100）联合 PD-1 抑制剂 Spartalizumab 治疗晚期/转移性实体瘤或淋巴瘤：一项开放标签、多中心、Ib 期研究。
Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study.
机构信息
The University of Texas MD Anderson Cancer Center, Houston, Texas.
The University of Chicago, Chicago, Illinois.
出版信息
Clin Cancer Res. 2023 Jan 4;29(1):110-121. doi: 10.1158/1078-0432.CCR-22-2235.
PURPOSE
The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas.
PATIENTS AND METHODS
Patients were treated with weekly intratumoral injections of MIW815 (50-3,200 μg) on a 3-weeks-on/1-week-off schedule or once every 4 weeks, plus a fixed dose of spartalizumab (400 mg) intravenously every 4 weeks.
RESULTS
Common adverse events were pyrexia (n = 23; 22%), injection site pain (n = 21; 20%), and diarrhea (n = 12; 11%). Overall response rate was 10.4%. The MTD was not reached. Pharmacodynamic biomarker analysis demonstrated on-target activity.
CONCLUSIONS
The combination of MIW815 and spartalizumab was well tolerated in patients with advanced/metastatic cancers, including in patients with anti-PD-1 refractory disease. Minimal antitumor responses were seen.
目的
干扰素基因刺激物（STING）是一种跨膜蛋白，在肿瘤的免疫反应中发挥作用。单一制剂 STING 激动剂 MIW815（ADU-S100）已显示出免疫激活作用，但抗肿瘤活性有限。这项 Ib 期、多中心、剂量递增研究评估了 MIW815 联合 PD-1 人源化 IgG4 抗体 spartalizumab（PDR001）在 106 例晚期实体瘤或淋巴瘤患者中的安全性和耐受性。
患者和方法
患者每周接受一次 MIW815（50-3200μg）瘤内注射，每 3 周一次/1 周一次，或每 4 周一次，同时每 4 周静脉注射固定剂量的 spartalizumab（400mg）。
结果
常见的不良反应有发热（n=23；22%）、注射部位疼痛（n=21；20%）和腹泻（n=12；11%）。总缓解率为 10.4%。未达到最大耐受剂量。药效学生物标志物分析显示有靶标活性。
结论
MIW815 和 spartalizumab 联合治疗晚期/转移性癌症患者耐受性良好，包括抗 PD-1 难治性疾病患者。观察到最小的抗肿瘤反应。
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