Purpose: Eftilagimod alpha (efti), a soluble LAG-3 protein, activates antigen-presenting cells (APC) and downstream T-cells. TACTI-002 (Part C) evaluated whether combining efti with pembrolizumab led to strong anti-tumor responses in 2nd line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients, while demonstrating good tolerability. Methods: In this multinational phase 2 trial using Simon’s 2-stage design, R/M HNSCC PD-L(1)-naïve patients who had failed first-line platinum-based therapy, unselected for PD-L1, received intravenous pembrolizumab (200 mg, Q3W) combined with subcutaneous efti (30 mg Q2W for 24 weeks and Q3W thereafter). The primary endpoint was objective response rate (ORR) per iRECIST by investigator assessment. Additional endpoints included duration of response (DoR), progression free survival (PFS), overall survival (OS) and tolerability. Pharmacodynamic effects (absolute lymphocyte count [ALC] and Th1 cytokine biomarkers [IFN-gamma/CXCL-10]) were evaluated in liquid biopsies. Results: Between Mar 2019 – Jan 2021, 39 patients were enrolled; 37 were evaluated for response. All patients received prior chemotherapy and 40.5% were pretreated with cetuximab. 53.1% of patients had PD-L1 CPS <20. With a median follow up of 38.8 months, ORR was 29.7%, including 13.5% complete responders. Median DoR was not reached. Rapid and sustained ALC increase was observed in patients who had an objective response. Th1 biomarkers increased sustainably after first treatment. No unexpected safety signals were observed. Conclusion: Efti plus pembrolizumab was safe and showed encouraging antitumor activity and pharmacodynamic effects in 2nd line HNSCC patients, thus supporting further evaluation of this combination in earlier treatment lines.

中文翻译：

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Eftilagimod α（可溶性 LAG-3 蛋白）联合派姆单抗作为转移性头颈鳞状细胞癌患者的二线治疗


目的：Eftilagimod alpha (efti) 是一种可溶性 LAG-3 蛋白，可激活抗原呈递细胞 (APC) 和下游 T 细胞。 TACTI-002（C 部分）评估了 efti 与派姆单抗联合使用是否会在二线复发或转移性头颈鳞状细胞癌 (R/M HNSCC) 患者中产生强烈的抗肿瘤反应，同时表现出良好的耐受性。方法：在这项采用 Simon 2 阶段设计的多国 2 期试验中，一线铂类治疗失败的 R/M HNSCC PD-L(1) 初治患者（未选择 PD-L1）接受静脉注射派姆单抗（200 mg，Q3W）联合皮下efti（30 mg Q2W，持续24周，此后Q3W）。主要终点是研究者评估的每个 iRECIST 的客观缓解率 (ORR)。其他终点包括缓解持续时间 (DoR)、无进展生存期 (PFS)、总生存期 (OS) 和耐受性。在液体活检中评估药效效应（绝对淋巴细胞计数 [ALC] 和 Th1 细胞因子生物标志物 [IFN-gamma/CXCL-10]）。结果：2019年3月至2021年1月期间，共有39名患者入组；评估了 37 人的反应。所有患者均接受过既往化疗，其中 40.5% 接受西妥昔单抗预处理。 53.1% 的患者患有 PD-L1 CPS <20。中位随访时间为 38.8 个月，ORR 为 29.7%，其中完全缓解率为 13.5%。未达到 DoR 中位数。在有客观反应的患者中观察到 ALC 快速且持续增加。首次治疗后 Th1 生物标志物持续增加。没有观察到意外的安全信号。结论：Efti 联合派姆单抗在二线 HNSCC 患者中是安全的，并且显示出令人鼓舞的抗肿瘤活性和药效学作用，因此支持在早期治疗线中进一步评估该组合。