Breast Cancer Research Program, Sarah Cannon Research Institute, Nashville, TN 37203, USA.
Medicine Department, Washington University School of Medicine, St Louis, MO 63110, USA.
Future Oncol. 2024;20(32):2447-2455. doi: 10.1080/14796694.2024.2377530. Epub 2024 Jul 29.
Vepdegestrant (ARV-471) is an oral PROTAC ER degrader that binds an E3 ubiquitin ligase and ER to directly trigger ubiquitination of ER and its subsequent proteasomal degradation. In a first-in-human Phase I/II study, vepdegestrant monotherapy was well tolerated with clinical activity in pretreated patients with ER+/HER2- advanced breast cancer. The global, randomized Phase III VERITAC-2 study compares efficacy and safety of vepdegestrant versus fulvestrant in adults with ER+/HER2- advanced breast cancer after treatment with a CDK4/6 inhibitor plus endocrine therapy. Progression-free survival by blinded independent central review (primary end point) will be assessed in the intention-to-treat population and mutation-positive subpopulation. Secondary end points include overall survival, tumor response, safety, pharmacokinetics, patient-reported outcomes, and circulating tumor DNA biomarkers. NCT05654623 (ClinicalTrials.gov).
Vepdegestrant（ARV-471）是一种口服 PROTAC ER 降解剂，它可以结合一种 E3 泛素连接酶和 ER，直接触发 ER 的泛素化及其随后的蛋白酶体降解。在一项首次人体的 I/II 期研究中，vepdegestrant 单药治疗在先前接受过治疗的 ER+/HER2-晚期乳腺癌患者中具有良好的耐受性和临床活性。全球、随机的 III 期 VERITAC-2 研究比较了 vepdegestrant 与氟维司群在 CDK4/6 抑制剂加内分泌治疗后治疗的 ER+/HER2-晚期乳腺癌成人患者中的疗效和安全性。通过盲法独立中心评估（主要终点）将在意向治疗人群和突变阳性亚组中评估无进展生存期。次要终点包括总生存期、肿瘤反应、安全性、药代动力学、患者报告结果和循环肿瘤 DNA 生物标志物。NCT05654623（ClinicalTrials.gov）。
