Wang J, Zhang Y, Bai R, Wu Y, Tong Z, Liu A, Zhang Y, Wang H, Wu X, Cheng Y, Yang H, Zhou Q, Xing X, Chen X, Qiu F, Ma F
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Department of Medical Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
ESMO Open. 2025 May;10(5):105059. doi: 10.1016/j.esmoop.2025.105059. Epub 2025 May 12.
ESG401 is a further optimized antibody-drug conjugate comprising a humanized anti-trophoblast cell-surface antigen 2 immunoglobulin G1 monoclonal antibody conjugated to SN-38, a topoisomerase I inhibitor, via a proprietary novel stable linker. The analysis aimed to explore the efficacy of ESG401 in human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) patients with brain metastases (BMs), a population urging significant clinical need with limited systematic treatment options.
This subgroup analysis was conducted as part of an open-label, multi-dose, dose-escalation, and cohort-expansion multicenter phase I trial. Eligible participants were aged 18-75 years and had locally advanced or metastatic solid tumors. For this subgroup analysis, patients with histologically confirmed HER2-negative BC and BMs were enrolled. Efficacy endpoints included overall objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS). Intracranial-specific endpoints included intracranial ORR (iORR), intracranial DCR (iDCR), and intracranial PFS. This trial is registered at ClinicalTrials.gov, NCT04892342.
Among 17 patients with efficacy-evaluable BMs, the iORR was 41% (7/17) [95% confidence interval (CI) 18.4% to 67.1%] including 3 patients achieving an intracranial complete response. The iDCR was 76% (13/17) (95% CI 50.1% to 93.2%). The overall ORR was 53% (9/17) (95% CI 27.8% to 77.0%), the overall DCR was 71% (12/17) (95% CI 44.0% to 89.7%), and the medium PFS was 5.7 months. The safety profile was consistent with previous reports.
These findings suggest that ESG401 is a promising and well-tolerated treatment option for BMs.
ESG401是一种经过进一步优化的抗体药物偶联物，它由一种人源化抗滋养层细胞表面抗原2免疫球蛋白G1单克隆抗体与拓扑异构酶I抑制剂SN-38通过一种专有的新型稳定连接子偶联而成。该分析旨在探究ESG401在伴有脑转移（BM）的人表皮生长因子受体2（HER2）阴性乳腺癌（BC）患者中的疗效，这是一个临床需求迫切但系统治疗选择有限的人群。
该亚组分析是一项开放标签、多剂量、剂量递增及队列扩展的多中心I期试验的一部分。符合条件的参与者年龄在18至75岁之间，患有局部晚期或转移性实体瘤。对于该亚组分析，纳入了组织学确诊为HER2阴性BC且伴有BM的患者。疗效终点包括总体客观缓解率（ORR）、疾病控制率（DCR）和无进展生存期（PFS）。颅内特异性终点包括颅内ORR（iORR）、颅内DCR（iDCR）和颅内PFS。该试验已在ClinicalTrials.gov注册，编号为NCT04892342。
在17例具有疗效评估价值的BM患者中，iORR为41%（7/17）[95%置信区间（CI）18.4%至67.1%]，其中3例患者实现颅内完全缓解。iDCR为76%（13/17）（95%CI 50.1%至93.2%）。总体ORR为53%（9/17）（95%CI 27.8%至77.0%），总体DCR为71%（12/17）（95%CI 44.0%至89.7%），中位PFS为5.7个月。安全性概况与先前报告一致。
这些发现表明ESG401是一种有前景且耐受性良好的BM治疗选择。
