Department of Medicine, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA.
Yale Cancer Center, New Haven, CT.
J Clin Oncol. 2024 Jul 1;42(19):2281-2294. doi: 10.1200/JCO.23.01909. Epub 2024 Apr 23.
Datopotamab deruxtecan (Dato-DXd) is an antibody-drug conjugate consisting of a humanized antitrophoblast cell-surface antigen 2 (TROP2) monoclonal antibody linked to a potent, exatecan-derived topoisomerase I inhibitor payload via a plasma-stable, selectively cleavable linker.
TROPION-PanTumor01 (ClinicalTrials.gov identifier: NCT03401385) is a phase I, dose-escalation, and dose-expansion study evaluating Dato-DXd in patients with previously treated solid tumors. The primary study objective was to assess the safety and tolerability of Dato-DXd. Secondary objectives included evaluation of antitumor activity and pharmacokinetics. Results from patients with advanced/metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer (BC) or triple-negative BC (TNBC) are reported.
At data cutoff (July 22, 2022), 85 patients (HR+/HER2- BC = 41, and TNBC = 44) had received Dato-DXd. The objective response rate by blinded independent central review was 26.8% (95% CI, 14.2 to 42.9) and 31.8% (95% CI, 18.6 to 47.6) for patients with HR+/HER2- BC and TNBC, respectively. The median duration of response was not evaluable in the HR+/HER2- BC cohort and 16.8 months in the TNBC cohort. The median progression-free survival in patients with HR+/HER2- BC and TNBC was 8.3 and 4.4 months, respectively. All-cause treatment-emergent adverse events (TEAEs; any grade, grade ≥3) were observed in 100% and 41.5% of patients with HR+/HER2- BC and 100% and 52.3% of patients with TNBC. Stomatitis was the most common TEAE (any grade, grade ≥3) in both HR+/HER2- BC (82.9%, 9.8%) and TNBC (72.7%, 11.4%) cohorts.
In patients with heavily pretreated advanced HR+/HER2- BC and TNBC, Dato-DXd demonstrated promising clinical activity and a manageable safety profile. Dato-DXd is currently being evaluated in phase III studies.
Datopotamab deruxtecan（Dato-DXd）是一种抗体药物偶联物，由一种人源化抗滋养层细胞表面抗原 2（TROP2）单克隆抗体与一种通过血浆稳定的、选择性裂解的连接子连接的强效依替康衍生的拓扑异构酶 I 抑制剂有效载荷组成。
TROPION-PanTumor01（ClinicalTrials.gov 标识符：NCT03401385）是一项 I 期、剂量递增和剂量扩展研究，评估了既往治疗过的实体瘤患者中 Dato-DXd 的安全性和耐受性。主要研究目的是评估 Dato-DXd 的安全性和耐受性。次要目标包括评估抗肿瘤活性和药代动力学。报告了晚期/转移性激素受体阳性/人表皮生长因子受体 2 阴性（HR+/HER2-）乳腺癌（BC）或三阴性 BC（TNBC）患者的结果。
截至数据截止日期（2022 年 7 月 22 日），85 名患者（HR+/HER2-BC=41 名，TNBC=44 名）接受了 Dato-DXd 治疗。盲法独立中心审查的客观缓解率分别为 HR+/HER2-BC 患者的 26.8%（95%CI，14.2 至 42.9）和 TNBC 患者的 31.8%（95%CI，18.6 至 47.6）。HR+/HER2-BC 队列中不可评估中位缓解持续时间，TNBC 队列中为 16.8 个月。HR+/HER2-BC 和 TNBC 患者的中位无进展生存期分别为 8.3 个月和 4.4 个月。HR+/HER2-BC 和 TNBC 患者的所有治疗相关不良事件（任何级别、≥3 级）发生率均为 100%和 41.5%，分别为 100%和 52.3%。HR+/HER2-BC（任何级别、≥3 级）和 TNBC（任何级别、≥3 级）队列中最常见的治疗相关不良事件（TEAE）均为口腔炎（分别为 82.9%，9.8%和 72.7%，11.4%）。
在既往接受过多线治疗的晚期 HR+/HER2-BC 和 TNBC 患者中，Dato-DXd 显示出有前景的临床活性和可管理的安全性特征。Dato-DXd 目前正在 III 期研究中进行评估。
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