Vepdegestrant(ARV-471)是一种口服PROTACER降解剂,可结合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。在一项首次进入人类的I/II期研究中,在ER+/HER2-晚期乳腺癌患者中,vepdegestrant单药治疗的临床活性耐受性良好。全球,随机III期VERITAC-2研究比较了在使用CDK4/6抑制剂加内分泌治疗后,Vepdegestrant与氟维司群在ER+/HER2-晚期乳腺癌成人患者中的疗效和安全性.将在意向治疗人群和ESR1突变阳性亚群中评估盲化独立中央审查(主要终点)的无进展生存率。次要终点包括总生存期,肿瘤反应,安全,药代动力学,患者报告的结果,和循环肿瘤DNA生物标志物。临床试验注册:NCT05654623(ClinicalTrials.gov)。
VERITAC-2是一项比较vepdegestrant的临床试验,一种降解雌激素受体的新药,对于ER+/HER2-晚期乳腺癌患者的现有治疗称为氟维司群:雌激素受体阳性(ER+)/人类表皮生长因子受体2阴性(HER2-)乳腺癌在雌激素反应中生长,体内的激素,并且具有低水平或没有HER2蛋白。患有ER+/HER2-晚期乳腺癌的人,传播到身体的另一部分,或不能通过手术切除通常用细胞周期蛋白依赖性激酶(CDK)4/6抑制剂和内分泌疗法治疗,但是他们的癌症可能会在这些治疗上变得更糟,需要新的治疗方法。Fulvestrant,一种附着在雌激素受体上的内分泌疗法,降低雌激素对肿瘤的影响,可以减缓或阻止癌症的生长。Vepdegestrant,一种新药正在测试ER+乳腺癌,是一种PROtesolutionTogeting嵌合体(PROTAC)蛋白质降解剂,它附着在雌激素受体上,并使它们被标记为通过细胞的天然蛋白质处置系统去除。通过去除雌激素受体,vepdegestrant可能导致肿瘤停止生长或缩小。本文介绍了VERITAC-2期临床研究,比较了Vepdegestrant与氟维司群在先前接受CDK4/6抑制剂和内分泌疗法治疗的ER/HER2晚期乳腺癌患者中的应用。患者将被随机分配接受vepdegestrant(每天口服一次的药丸)或氟维司群(注射到肌肉中)。这项研究的目的是找出使用vepdegegestrant或fulvestrant的癌症没有恶化的人的寿命。VERITAC-2还将研究人们在研究期间的寿命,人们可能会经历的副作用,以及整个研究过程中人们的整体幸福感。
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 ESR1 mutation-positive subpopulation. Secondary end points include overall survival, tumor response, safety, pharmacokinetics, patient-reported outcomes, and circulating tumor DNA biomarkers.Clinical trial registration: NCT05654623 (ClinicalTrials.gov).
VERITAC-2 is a clinical trial comparing vepdegestrant, a new drug that degrades estrogen receptors, to an existing treatment called fulvestrant in patients with ER+/HER2- advanced breast cancer: Estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer grows in response to estrogen, a hormone in the body, and has low levels or no HER2 protein. People living with ER+/HER2- advanced breast cancer that has grown, spread to another part of the body, or cannot be removed by surgery are often treated with cyclin-dependent kinase (CDK) 4/6 inhibitors and endocrine therapies, but their cancer may get worse on these treatments and new treatments are needed. Fulvestrant, an endocrine therapy that attaches to estrogen receptors, lowers estrogen\'s effect on tumors and can slow or stop cancer growth. Vepdegestrant, a new medicine being tested for ER+ breast cancer, is a PROteolysis TArgeting Chimera (PROTAC) protein degrader that attaches to estrogen receptors and causes them to be tagged for removal by the cell\'s natural protein disposal system. By removing estrogen receptors, vepdegestrant may cause tumors to stop growing or shrink.This paper describes the Phase III VERITAC-2 clinical study comparing vepdegestrant versus fulvestrant in people living with ER+/HER2- advanced breast cancer previously treated with a CDK4/6 inhibitor and endocrine therapy.Patients will be randomly assigned to receive vepdegestrant (a pill taken once daily by mouth) or fulvestrant (a shot given into the muscle). The purpose of the study is to find out how long people live without their cancer getting worse with vepdegestrant or fulvestrant. VERITAC-2 will also look at how long people live during the study, side effects people may experience, and the overall well-being of people throughout the study.