VERITAC-2: A global, randomized phase 3 study of ARV-471, a proteolysis targeting chimera (PROTAC) estrogen receptor (ER) degrader, vs fulvestrant in ER+/human epidermal growth factor receptor 2 (HER2)- advanced breast cancer.

• DOI: 10.1200/jco.2023.41.16_suppl.tps1122
• Publication Date: 2023-06-04T14:10:33Z
• Authors: Mario Campone; Cynthia X. Ma; Michelino De Laur...; Hiroji Iwata; Sara A. Hurvitz; Seth Andrew Wander; Michael A. Danso; Dongrui Ray Lu; Julia Perkins Smith; Yuan Liu; Lana Tran; Sibyl Anderson; Erika P. Hamilton
• Keywords: Fulvestrant; Tolerability; Palbociclib; Combination therapy

TPS1122 Background: ARV-471 is an oral PROTAC ER degrader that binds to and degrades wild-type clinically relevant mutants. directly recruits the ubiquitin-proteasome system degrade ER, whereas selective degraders (SERDs) indirectly cause degradation. In a first-in-human phase 1/2 study, monotherapy was well tolerated showed clinical activity in heavily pretreated patients with ER+/HER2- advanced breast cancer. The 3 dose (200 mg once daily [QD]) chosen due comparable efficacy favorable tolerability relative 500 QD robust degradation paired tumor biopsies. randomized VERITAC-2 study (NCT05654623) will compare safety of vs SERD fulvestrant cancer after prior combination cyclin-dependent kinase 4 6 (CDK4/6) inhibitor therapy endocrine (ET). Methods: Eligible (aged ≥18 years) have confirmed diagnosis locoregional recurrent or metastatic not amenable surgical resection radiation; 1 line CDK4/6 ET; ≤1 additional most recent ET given for ≥6 months before disease progression; radiological progression during last therapy. Prior chemotherapy locally setting are permitted. Patients (N~560) 1:1 receive 200 orally continuously intramuscularly on days 15 first 28-day cycle day subsequent cycles; stratified by ESR1 mutation status presence visceral disease. primary endpoint, progression-free survival, be assessed blinded independent central review intention-to-treat population sub-population. Secondary outcome measures include overall antitumor (objective response rate, duration response, benefit rate), safety, quality life assessments. Clinical trial information: NCT05654623 .