Eftilagimod alpha (efti) 是一种可溶性 LAG-3 蛋白和 MHC II 类激动剂，可增强先天性和适应性免疫。 AIPAC 评估了 efti 加紫杉醇治疗主要内分泌耐药、激素受体阳性、HER2 阴性转移性乳腺癌（ET 耐药 HR HER2- MBC）患者的安全性和有效性。HR HER2- MBC 女性按 1:1 随机分配至每周静脉注射紫杉醇 (80 mg/m2) 和每 2 周皮下注射 efti (30 mg) 或安慰剂，持续 6 个 4 周周期，然后每月皮下注射 efti (30 mg) 或安慰剂维持。主要终点是通过盲法独立中央审查得出的无进展生存期（PFS）。次要终点包括总生存期（OS）、安全性/耐受性、药代动力学/药效学和生活质量。探索性终点包括细胞生物标志物。114 名患者接受 efti，112 名患者接受安慰剂。中位年龄为 60 岁（91.6% 患有内脏疾病，84.1% 患有 ET 耐药，44.2% 曾接受过 CDK4/6 抑制剂治疗）。 efti 和安慰剂的中位无进展生存期 (PFS) 为 7.3 个月，相似。 efti 的中位 OS 没有显着改善（20.4 个月与 17.5 个月；HR，0.88；P = 0.197），但对于预定义的探索性亚组而言变得显着。 EORTC QLQC30-B23 全球健康状况在 efti 组中保持不变，但在安慰剂组中恶化。 EFTI 增加了绝对淋巴细胞、单核细胞和次要靶细胞（CD4、CD8）计数、血浆 IFN-γ 和 CXCL10 水平。尽管未达到主要终点 PFS，但 AIPAC 证实了 efti 的预期药效作用并表现出出色的安全性。全球总体生存率并未显着改善（差异为 2.9 个月），但在探索性生物标志物亚组中显着改善，需要进一步研究以阐明 efti 在 ET 耐药 HER2-MBC 患者中的作用。

Eftilagimod alpha (efti), a soluble LAG-3 protein and MHC class II agonist, enhances innate and adaptive immunity. AIPAC evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC).Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance. Primary endpoint was progression-free survival (PFS) by blinded independent central review. Secondary endpoints included overall survival (OS), safety/tolerability, pharmacokinetics/pharmacodynamics, and quality of life. Exploratory endpoints included cellular biomarkers.114 patients received efti and 112, placebo. Median age was 60 years (91.6% visceral disease, 84.1% ET-resistant, 44.2% with previous CDK4/6 inhibitor treatment). Median PFS at 7.3 months was similar for efti and placebo. Median OS was not significantly improved for efti (20.4 vs. 17.5 months; HR, 0.88; P = 0.197), but became significant for predefined exploratory subgroups. EORTC QLQC30-B23 global health status was sustained for efti but deteriorated for placebo. Efti increased absolute lymphocyte, monocyte and secondary target cell (CD4, CD8) counts, plasma IFN-γ and CXCL10 levels.Although the primary endpoint, PFS, was not met, AIPAC confirmed expected pharmacodynamic effects and demonstrated excellent safety profile for efti. Overall survival was not significantly improved globally (2.9-month difference), but was significantly improved in exploratory biomarker subgroups, warranting further studies to clarify efti's role in patients with ET-resistant HER2- MBC.