Recruiting

Phase 2

Biomarker-Directed TherapiesEvolutionary Clinical Trial for Novel Biomarker-Driven Therapies

Sponsor:

UNC Lineberger Comprehensive Cancer Center

Code:

NCT07340541

Conditions

Breast Cancer

Metastatic Breast Cancer

Triple Negative Breast Cancer

Estrogen-receptor-positive Breast Cancer

Hormone Receptor Negative Breast Carcinoma

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

SERD* + abemaciclib

SERD* + everolimus

SERD* + everolimus or capecitabine

SOC

Antiandrogen

Study Details

Brief summary:

This is a multicenter, multi-arm, biomarker-stratified trial designed to evaluate biomarker-directed therapies in patients with estrogen receptor-positive/hormone receptor-negative (ER+/HR-) and triple-negative (TN) metastatic breast cancer (MBC). The trial integrates both retrospective and prospective data collection, including archival tumor tissue, medical record abstraction, and prospective tumor and blood sampling prior to initiation of protocol directed treatment. Based on biomarker subtype, participants will receive standard of care therapy. Liquid biopsy will be collected on Cycle 2 Day 1, and then liquid biopsy, imaging and clinical data will be collected at each re-staging. Treatment will continue until discontinuation for progression, toxicity or at the discretion of the treating physician.

Conditions

Breast Cancer

Metastatic Breast Cancer

Triple Negative Breast Cancer

Estrogen-receptor-positive Breast Cancer

Hormone Receptor Negative Breast Carcinoma

Study ID

NCT07340541

Start date

Feb 16, 2026

Status verified date

Jul, 2026

Completion date

Jun 2, 2031

Anticipated

Primary completion date

Jun 2, 2031

Anticipated

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Written informed consent obtained to participate in the study and HIPAA authorization for release of personal health information.
Subject is willing and able to comply with study procedures based on the judgement of the investigator.
Age ≥ 18 years of age at the time of consent
ECOG Performance Status of 0-2 (see APPENDIX A: ECOG Performance Status Scale).
Patients must fulfill all eligibility criteria outlined in the LCCC2521 Parent Protocol and consented to LCCC2521 Parent Protocol

Exclusion Criteria:

Inaccessible metastatic lesion to research biopsy
Subject has already initiated 2nd line therapy
Concurrent disease or condition that in the opinion of the treating oncologist renders the patient inappropriate for study participation

Study Design

Enrollment

700 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Cohort 1 Arm A

ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant positive or negative and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion negative.

experimental: Cohort 1- Arm B

experimental: Cohort 2 Arm A

ER+ (Estrogen Receptor Positive) and HER2- (Human Epidermal Growth Factor Receptor 2 Negative). ESR1 mutant negative or positive, and Phosphatidylinositol 3-kinase catalytic subunit alpha / AKT serine/threonine kinase / PTEN loss or deletion positive.

experimental: Cohort 2 Arm B

active comparator: Cohort 3

Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR - = Androgen Receptor negative, PD-L1 (Programmed Death-Ligand 1) positive or negative.

experimental: Cohort 4

Triple-Negative Breast Cancer (TNBC): ER- (Estrogen receptor negative), PR- (Progesterone receptor negative), HER2- HER2 negative. AR + = Androgen Receptor positive, PD-L1 (Programmed Death-Ligand 1) positive or negative.

Interventions

SERD* + abemaciclib

Investigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy.

SERD* + everolimus

Investigators choice Selective Estrogen Receptor Degrader + everolimus therapy.

SERD* + everolimus or capecitabine

Investigators choice Selective Estrogen Receptor Degrader + everolimus or capecitabine therapy.

SOC

standard-of-care (SOC) chemotherapy in breast cancer

Antiandrogen

Antiandrogen therapy

Primary outcome measure

Intra-Individual Progression-Free Survival (PFS) [ Time Frame: Up to 5 years ]

Central Contacts and Locations

Central contacts

Emily L Schworer

919-984-0000 emily_lane@med.unc.edu

Ana Gallegos

ana_gallegos@med.unc.edu

Locations

Yale Cancer Center Clinical Trials Office

Recruiting

New Haven, Connecticut, United States, 06519

Contacts

Sarah Mooney

sarah.mooney@yale.edu

Principal Investigator:

Eric Winer, MD

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Cesar Santa-Maria, MD

jhcccro@jhmi.edu

Principal Investigator:

Cesar Santa-Maria, MD

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Recruiting

Chapel Hill, North Carolina, United States, 27599-7305

Contacts

Lisa A. Carey, MD

919-966-4431

Principal Investigator:

Lisa A Carey, MD

More Information

Sponsor

UNC Lineberger Comprehensive Cancer Center

Last update posted

Jul 31, 2026

Last verified

Jul, 2026

Keywords

biomarker directed therapies
biomarker stratified trial

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by UNC Lineberger Comprehensive Cancer Center on 2026-07-31.