Novel TROP2 antibody–drug conjugates for treatment of HER2-negative metastatic breast cancer patients with brain metastases: a promising option☆

IF 7.1 2区医学 Q1 ONCOLOGY

ESMO Open Pub Date : 2025-05-01 DOI:10.1016/j.esmoop.2025.105059

J. Wang , Y. Zhang , R. Bai , Y. Wu , Z. Tong , A. Liu , Y. Zhang , H. Wang , X. Wu , Y. Cheng , H. Yang , Q. Zhou , X. Xing , X. Chen , F. Qiu , F. Ma

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Abstract

Background

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.

Patients and methods

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.

Results

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.

Conclusions

These findings suggest that ESG401 is a promising and well-tolerated treatment option for BMs.

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新型TROP2抗体-药物偶联物治疗her2阴性转移性乳腺癌脑转移患者：一个有希望的选择☆

desg401是一种进一步优化的抗体-药物偶联物，包括人源化的抗滋养层细胞表面抗原2免疫球蛋白G1单克隆抗体，通过专有的新型稳定连接物与拓扑异构酶I抑制剂SN-38偶联。该分析旨在探讨ESG401在人表皮生长因子受体2 （HER2）阴性乳腺癌（BC）脑转移（BMs）患者中的疗效，这是一个迫切需要显着临床需求且系统治疗选择有限的人群。患者和方法该亚组分析是一项开放标签、多剂量、剂量递增和队列扩展的多中心I期试验的一部分。符合条件的参与者年龄在18-75岁之间，患有局部晚期或转移性实体瘤。在这个亚组分析中，纳入了组织学证实her2阴性的BC和脑转移患者。疗效终点包括总客观缓解率（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NCT04892342。结果在17例可评估疗效的脑转移患者中，iORR为41%(7/17)[95%置信区间（CI） 18.4%至67.1%]，其中3例患者达到颅内完全缓解。iDCR为76% (13/17)（95% CI 50.1% ~ 93.2%）。总ORR为53% (9/17)(95% CI 27.8% ~ 77.0%)，总DCR为71% (12/17)(95% CI 44.0% ~ 89.7%)，中期PFS为5.7个月。安全概况与以前的报告一致。这些发现表明ESG401是脑转移的一种有前景且耐受性良好的治疗选择。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ESMO Open Medicine-Oncology

CiteScore

11.70

自引率

2.70%

发文量

255

审稿时长

10 weeks

期刊介绍： ESMO Open is the online-only, open access journal of the European Society for Medical Oncology (ESMO). It is a peer-reviewed publication dedicated to sharing high-quality medical research and educational materials from various fields of oncology. The journal specifically focuses on showcasing innovative clinical and translational cancer research. ESMO Open aims to publish a wide range of research articles covering all aspects of oncology, including experimental studies, translational research, diagnostic advancements, and therapeutic approaches. The content of the journal includes original research articles, insightful reviews, thought-provoking editorials, and correspondence. Moreover, the journal warmly welcomes the submission of phase I trials and meta-analyses. It also showcases reviews from significant ESMO conferences and meetings, as well as publishes important position statements on behalf of ESMO. Overall, ESMO Open offers a platform for scientists, clinicians, and researchers in the field of oncology to share their valuable insights and contribute to advancing the understanding and treatment of cancer. The journal serves as a source of up-to-date information and fosters collaboration within the oncology community.