Design of SERENA-6, a phase III switching trial of camizestrant in <i>ESR1</i> -mutant breast cancer during first-line treatment
Nicholas C. Turner, Cynthia Huang Bartlett, Kevin Kalinsky, Massimo Cristofanilli, Giampaolo Bianchini, Stephen Chia, Hiroji Iwata, Wolfgang Janni, X. Cynthia, Erica L. Mayer, Yeon Hee Park, Stephen B. Fox, Xiaochun Liu, Sasha McClain, François‐Clément Bidard
Abstract
ESR1 mutation (ESR1m) is a frequent cause of acquired resistance to aromatase inhibitor (AI) plus cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), which is a first-line therapy for hormone-receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Camizestrant is a next-generation oral selective estrogen receptor degrader (SERD) that in a phase II study significantly improved progression-free survival (PFS) over fulvestrant (also a SERD) in ER+/HER2- ABC. SERENA-6 (NCT04964934) is a randomized, double-blind, phase III study evaluating the efficacy and safety of switching from an AI to camizestrant, while maintaining the same CDK4/6i, upon detection of ESR1m in circulating tumor DNA before clinical disease progression on first-line therapy for HR+/HER2- ABC. The aim is to treat ESR1m clones and extend the duration of control of ER-driven tumor growth, delaying the need for chemotherapy. The primary end point is PFS; secondary end points include chemotherapy-free survival, time to second progression event (PFS2), overall survival, patient-reported outcomes and safety.