TROPION-Breast03：一项关于datopotamab deruxtecan联合或不联合度伐利尤单抗用于新辅助治疗后手术切除时有三阴性乳腺癌和残留浸润性疾病患者的随机III期全球试验。
TROPION-Breast03: a randomized phase III global trial of datopotamab deruxtecan ± durvalumab in patients with triple-negative breast cancer and residual invasive disease at surgical resection after neoadjuvant therapy.
作者信息
Bardia Aditya, Pusztai Lajos, Albain Kathy, Ciruelos Eva Maria, Im Seock-Ah, Hershman Dawn, Kalinsky Kevin, Isaacs Claudine, Loirat Delphine, Testa Laura, Tokunaga Eriko, Wu Jiong, Dry Hannah, Barlow William, Kozarski Robert, Maxwell Micah, Harbeck Nadia, Sharma Priyanka
机构信息
Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA.
Yale University, New Haven, CT, USA.
出版信息
Ther Adv Med Oncol. 2024 Apr 29;16:17588359241248336. doi: 10.1177/17588359241248336. eCollection 2024.
BACKGROUND
Despite advances in the treatment of early triple-negative breast cancer (TNBC), patients with residual invasive disease after neoadjuvant therapy have a high risk of disease recurrence and worse survival outcomes than those who have pathological complete response (pCR). Improving outcomes in early TNBC remains an unmet need requiring new adjuvant treatment approaches. Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate comprising a humanized anti-trophoblast cell-surface antigen 2 immunoglobulin G1 (IgG1) monoclonal antibody attached a plasma-stable, cleavable linker to a potent topoisomerase I inhibitor payload, with activity observed in advanced TNBC.
OBJECTIVES
TROPION-Breast03 is an ongoing phase III study evaluating the efficacy and safety of Dato-DXd alone or combined with durvalumab standard-of-care therapy as adjuvant treatment in patients with stage I-III TNBC with residual invasive disease at surgical resection following neoadjuvant treatment.
METHODS AND DESIGN
Eligible patients, aged ⩾18 years, will be randomized in a 2:1:2 ratio to receive Dato-DXd [6 mg/kg intravenously (IV) every 3 weeks (Q3W); eight cycles] and durvalumab (1120 mg IV Q3W; nine cycles), Dato-DXd monotherapy (6 mg/kg IV Q3W), or investigator's choice of therapy (ICT; capecitabine, pembrolizumab, or capecitabine and pembrolizumab). The primary endpoint is invasive disease-free survival (iDFS) for Dato-DXd and durvalumab ICT. Key secondary endpoints include safety, distant disease-free survival, and overall survival for Dato-DXd and durvalumab ICT and iDFS for Dato-DXd monotherapy ICT.
ETHICS
TROPION-Breast03 will be approved by the independent ethics committees or institutional review boards at each study site. All study participants will provide written informed consent.
DISCUSSION
TROPION-Breast03 will help define the potential role of Dato-DXd in the treatment of patients with early-stage TNBC who do not have pCR after neoadjuvant therapy.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT05629585 (registration date: 29 November 2022).
背景
尽管早期三阴性乳腺癌（TNBC）的治疗取得了进展，但新辅助治疗后仍有残留浸润性疾病的患者疾病复发风险高，且生存结果比病理完全缓解（pCR）的患者更差。改善早期TNBC的治疗结果仍然是一项未满足的需求，需要新的辅助治疗方法。达泊托单抗（Datopotamab deruxtecan，Dato-DXd）是一种抗体药物偶联物，由人源化抗滋养层细胞表面抗原2免疫球蛋白G1（IgG1）单克隆抗体组成，通过血浆稳定、可裂解的连接子与一种强效拓扑异构酶I抑制剂有效载荷相连，在晚期TNBC中观察到其活性。
目的
TROPION-Breast03是一项正在进行的III期研究，评估Dato-DXd单药或与度伐利尤单抗联合作为标准治疗，用于新辅助治疗后手术切除时有残留浸润性疾病的I-III期TNBC患者的辅助治疗的疗效和安全性。
方法与设计
符合条件的年龄≥18岁的患者将按2:1:2的比例随机分组，接受Dato-DXd（每3周静脉注射6mg/kg，共8个周期）和度伐利尤单抗（每3周静脉注射1120mg，共9个周期）、Dato-DXd单药治疗（每3周静脉注射6mg/kg）或研究者选择的治疗（ICT；卡培他滨、帕博利珠单抗或卡培他滨与帕博利珠单抗联合）。主要终点是Dato-DXd联合度伐利尤单抗与ICT的无浸润性疾病生存期（iDFS）。关键次要终点包括安全性、远处无病生存期、Dato-DXd联合度伐利尤单抗与ICT的总生存期以及Dato-DXd单药治疗与ICT的iDFS。
伦理
TROPION-Breast03将获得各研究地点的独立伦理委员会或机构审查委员会的批准。所有研究参与者将提供书面知情同意书。
讨论
TROPION-Breast03将有助于确定Dato-DXd在治疗新辅助治疗后未达到pCR且处于早期TNBC患者中的潜在作用。
试验注册
ClinicalTrials.gov标识符：NCT05629585（注册日期：2022年11月29日）。
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