CHAPEL HILL, N.C. — The EVOLVE-BDT clinical trial opened for enrollment on February 16, 2026. The Phase 2 study (NCT07340541) is a multicenter, biomarker-stratified evolutionary trial evaluating second-line therapies in patients with estrogen receptor-positive, HER2-negative and triple-negative metastatic breast cancer.
EVOLVE-BDT (TBCRC Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies) is sponsored by UNC Lineberger Comprehensive Cancer Center in collaboration with the Translational Breast Cancer Research Consortium, the Breast Cancer Research Foundation, and the Advanced Research Projects Agency for Health (ARPA-H). The trial is led by principal investigator Lisa A. Carey, MD, at UNC Lineberger.
The platform design enables multiple biomarker-directed treatment arms to run within a shared parent infrastructure. Eligible participants have metastatic breast cancer that has progressed on first-line therapy but have not yet started second-line treatment. Based on biomarker subtype, patients receive standard-of-care or investigational regimens including selective estrogen receptor degraders combined with abemaciclib or everolimus, standard-of-care chemotherapy for triple-negative disease, or antiandrogen therapy for androgen receptor-positive triple-negative breast cancer.
Liquid biopsy is collected on cycle 2 day 1 and at each restaging, alongside imaging and clinical data, to track response and resistance longitudinally. The adaptive framework allows patients who progress to move into additional biomarker-driven sub-trials. Primary endpoints include intra-individual and between-arm progression-free survival, with secondary measures of objective response rate, duration of response, clinical benefit rate, and changes in circulating tumor DNA and transcriptomic profiles.
The trial aims to enroll approximately 700 participants across TBCRC sites, with UNC Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina currently recruiting. Exploratory objectives include using ctDNA and tissue multi-omics to model resistance mechanisms and inform AI-guided therapy selection.
Eligible patients are adults aged 18 or older with ER+/HER2- or triple-negative metastatic breast cancer who progressed on first-line therapy without having started second-line treatment. HER2-positive patients are excluded. Participants must consent to the parent protocol and provide archival or prospective tumor and blood samples before protocol-directed treatment begins.
For more information about EVOLVE-BDT, visit clinicaltrials.gov/study/NCT07340541 or UNC Lineberger clinical trials at unclineberger.org/patientcare/clinical-trials/clinical-trials.