154TiP TACTIVE-N: Open-label, randomized, noncomparative neoadjuvant phase 2 study of ARV-471, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, or anastrozole in postmenopausal women with ER+/human epidermal growth factor receptor 2 (HER2)- localized breast cancer

The orally administered PROTAC ER degrader ARV-471 demonstrated potent degradation and tumor growth inhibition, including regression, in preclinical models. In the first-in-human phase I/II study, once-daily (QD) monotherapy was well tolerated showed antitumor activity heavily pretreated patients with ER+/HER2- advanced breast cancer. Anastrozole, an aromatase inhibitor, is a standard treatment option for localized Here we describe open-label, randomized, noncomparative, multi-country II study (NCT05549505) to evaluate safety clinical of or anastrozole cancer amenable definitive surgical resection. following are eligible TACTIVE-N (N?150): postmenopausal women (aged ?18 years) histologically cytologically confirmed staining ?10% cell nuclei (Ki-67 score ?5%, T1c-T4c, N0-N2, M0 cancer). Patients bilateral ductal carcinoma situ, invasive cancer, prior excluded. will be randomized receive QD until resection approximately 5.5 months after starting (cycle 6, day 18 ± 10 days). primary objective effect on Ki-67 expression tumors 2 weeks treatment. Secondary objectives include safety, pathological response (pathologic stage, pathologic complete rate, modified preoperative endocrine prognostic index at time resection), (breast-conserving surgery radiographic rate during cycle best percentage change caliper measurement 6 1). NCT05549505. Medical Writing Support: Beth Sesler, PhD, Apollo Communications, funded by Arvinas Operations, Inc. Estrogen Receptor,