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Abstract：
Ieramilimab, a humanized anti-LAG-3 monoclonal antibody, was well tolerated in combination with the anti-PD-1 antibody spartalizumab in a phase 1 study. This phase 2 study aimed to further investigate the efficacy and safety of combination treatment in patients with selected advanced (locally advanced or metastatic) solid malignancies. Eligible patients with non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma (RCC), mesothelioma, and triple-negative breast cancer (TNBC) were grouped depending on prior anti-PD-1/L1 therapy (anti-PD-1/L1 naive or anti-PD-1/L1 pretreated). Patients received ieramilimab (400 mg) followed by spartalizumab (300 mg) every 3 weeks. The primary endpoint was objective response rate (ORR), along with safety, pharmacokinetics, and biomarker assessments. Of 235 patients, 142 were naive to anti-PD-1/L1 and 93 were pretreated with anti-PD-1/L1 antibodies. Durable responses (>24 months) were seen across all indications for patients naive to anti-PD-1/L1 and in melanoma and RCC patients pretreated with anti-PD1/L1. The most frequent study drug-related AEs were pruritus (15.5%), fatigue (10.6%), and rash (10.6%) in patients naive to anti-PD-1/L1 and fatigue (18.3%), rash (14.0%), and nausea (10.8%) in anti-PD-1/L1 pretreated patients. Biomarker assessment indicated higher expression of T-cell-inflamed gene signature at baseline among responding patients. Response to treatment was durable (>24 months) in some patients across all enrolled indications, and safety findings were in accordance with previous and current studies exploring LAG-3/PD-1 blockade.
摘要：
Ieramilimab,人源化抗LAG-3单克隆抗体，在1期研究中，与抗PD-1抗体司他珠单抗联合用药耐受性良好。这项2期研究旨在进一步研究联合治疗在选定的晚期（局部晚期或转移性）实体恶性肿瘤患者中的疗效和安全性。符合条件的非小细胞肺癌（NSCLC）患者，黑色素瘤，肾细胞癌（RCC），间皮瘤,和三阴性乳腺癌（TNBC）根据之前的抗PD-1/L1治疗（抗PD-1/L1未治疗或抗PD-1/L1预处理）进行分组。患者每3周接受ieramilimab（400mg），然后接受司他珠单抗（300mg）。主要终点是客观缓解率（ORR），还有安全,药代动力学，和生物标志物评估。235名患者中,142例未经抗PD-1/L1治疗，93例用抗PD-1/L1抗体预处理。在抗PD-1/L1未治疗的患者以及用抗PD1/L1预处理的黑素瘤和RCC患者的所有适应症中都可以看到持久的反应（>24个月）。最常见的研究药物相关不良事件是瘙痒（15.5%），疲劳(10.6%)，首次使用抗PD-1/L1和疲劳（18.3％）的患者出现皮疹（10.6％），皮疹（14.0%），抗PD-1/L1预处理患者的恶心（10.8%）。生物标记物评估表明，在有反应的患者中，基线时T细胞发炎的基因特征表达较高。在所有入选适应症中，一些患者对治疗的反应是持久的（>24个月），和安全性发现与以往和目前探索LAG-3/PD-1阻断的研究一致.
