Eftilagimod alpha (efti) 是一种人类主要组织相容性复合体II类激动剂，它能够激活抗原呈递细胞，从而引发更高的全身型1型辅助T细胞反应和更多的细胞毒性CD8+ T细胞激活。该I期试验评估了联合应用可溶性淋巴细胞活化基因3（LAG-3）蛋白efti和抗程序性死亡配体1（PD-L1）抗体avelumab对晚期实体肿瘤的给药情况。经过重度预处理的转移性实体瘤患者接受了静脉注射avelumab（800 mg）和皮下注射efti（6或30 mg）的联合治疗，共进行了最多12个周期的治疗，随后转为avelumab单药治疗。主要终点是评估联合应用efti和avelumab的建议II期剂量（RP2D）。 共有12名不同肿瘤类型的患者被招募入组（每组6名患者）。在治疗过程中，没有剂量限制性毒性反应发生，大多数不良事件的严重程度为1或2级。共有9起严重不良事件记录，其中2例导致了致命结局，但都与治疗无关。5名患者（42％）达到了部分缓解。中位无进展生存期为1.96个月，中位总生存期尚未达到，12个月生存率为75％。 皮下注射的efti联合avelumab耐受性良好，30 mg的efti被确定为RP2D。该治疗方法表现出良好的活性，值得在未来的II期试验中进一步研究。 版权所有 © 2023 作者。由Elsevier Ltd.发表。保留所有权利。

Eftilagimod alpha (efti) is a major histocompatibility complex class II agonist activating antigen-presenting cells which leads to greater systemic type 1 T helper response and more cytotoxic CD8+ T-cell activation. This phase I trial evaluated the administration of efti, a soluble lymphocyte activation gene-3 (LAG-3) protein, combined with the anti-programmed death-ligand 1 (PD-L1) antibody avelumab in advanced solid tumors.Patients with heavily pretreated metastatic solid tumors received intravenous avelumab (800 mg) combined with subcutaneously administered efti (6 or 30 mg) for up to 12 cycles, followed by avelumab monotherapy. The primary endpoint was the assessment of the recommended phase II dose (RP2D) of efti in combination with avelumab.Twelve patients with different tumor entities were enrolled (six patients in each cohort). During treatment, no dose-limiting toxicities occurred, and the severity of most adverse events was grade 1 or 2. In total, nine serious adverse events were documented, resulting in a fatal outcome in two cases, but none of them were assessed to be treatment related. Five patients (42%) achieved partial response. The median progression-free survival was 1.96 months and the median overall survival was not reached, with a 12-month survival rate of 75%.Subcutaneously administered efti plus avelumab was well tolerated, and efti of 30 mg was determined to be RP2D. The activity is promising and warrants further investigation in future phase II trials.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.