Study design of the phase III ADELA trial of elacestrant with or without everolimus in ESR1 -mutated ER+/HER2– advanced breast cancer after progression on endocrine therapy plus a CDK4/6 inhibitor
Year: 2026
Type: article
Study design: Study Protocol
Abstract: For patients with estrogen receptor-positive (ER+)/HER2-negative (HER2-) advanced breast cancer (aBC), endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i) is standard first-line treatment. However, ET resistance eventually develops, leading to disease progression. Mechanisms of endocrine resistance include PI3K/AKT/mTOR pathway constitutive activation and acquired mutations in the estrogen receptor 1 (ESR1) gene. Novel approaches are needed to improve outcomes for patients progressing on ET plus CDK4/6i. Elacestrant, a next-generation oral selective estrogen receptor degrader, is approved for patients with ER+/HER2- ESR1-mutated aBC after at least one line of ET, including a CDK4/6i. Everolimus, an mTORC1 inhibitor, is indicated in combination with exemestane for the treatment of postmenopausal women with ER+/HER2- aBC after progression on non-steroidal aromatase inhibitors. In the ELEVATE phase Ib/II trial, elacestrant plus everolimus showed a clinically meaningful progression-free survival (PFS) irrespective of ESR1 or PIK3CA mutation status in patients with ER+/HER2- aBC progressing after ET plus CDK4/6i. Here, we describe the design and methodology of ADELA, an international, multicenter, double-blind, placebo-controlled, randomized phase III trial evaluating elacestrant plus everolimus versus elacestrant plus placebo in patients with ER+/HER2-, ESR1-mutated aBC following ET plus CDK4/6i. The primary endpoint is PFS assessed by a blinded imaging review committee using RECIST v.1.1.Clinical trial registration www.clinicaltrials.gov identifier is NCT06382948; EU Clinical Trials identifier is EUCT 2024-512926-27-00.
Source: Future Oncology
Authors: José Manuel Pérez-García, Antonio Llombart-Cussac, Elena López-Miranda, Alfonso Cortes, Isabel Garcia-Fructuoso, Elena Galve-Calvo, Manuel Ruiz-Borrego, Alba Cochs, Antonia Perelló-Martorell, Serafin Morales, Laia Boronat Ruiz, Sara Marín-Liébana, Cristina Saavedra, Isabel Blancas, Carmen Hinojo, Mariana López Flores, Sylvain Ladoire, Peter Schmid, Gilles Freyer, Rui Rui Zhang, Daniel Alcalá-López, Juliana Carvalho-Santos, Olga Boix, Carlos H. Barrios, Giuseppe Curigliano, Rupert Bartsch, Anne Clair Hardy Bessard, Tomer Wasserman, Javier Cortés
Institutions: Universidad Cardenal Herrera CEU, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana, Hospital Arnau de Vilanova, Instituto Ramón y Cajal de Investigación Sanitaria, Hospital Universitario Ramón y Cajal, Hospital Clínic de Barcelona, Hospital de Basurto, Hospital Universitario Virgen del Rocío, Hospital Universitari Sant Joan de Reus, Hospital Universitario Son Espases, Hospital Universitari Arnau de Vilanova, Institut Català d'Oncologia, Universidad de Granada, Instituto de Investigación Biosanitaria de Granada, Marqués de Valdecilla University Hospital, Instituto de Investigación Marqués de Valdecilla, Hospital Universitario de León, Centre Georges François Leclerc, Queen Mary University of London, Barts Health NHS Trust, Barts Cancer Institute, Hospices Civils de Lyon, Hôpital Lyon Sud, Latin American Cooperative Oncology Group (LACOG), University of Milan, Medical University of Vienna, UniCancer Group, Menarini Group (Luxembourg), Menarini Group (Italy), Menarini Group (Germany)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7225004807