Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies

NCT07340541 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: LCCC2521-TBCRC-073(EVOLVE-BDT)140D042590009
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 2

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; Estrogen-receptor-positive Breast Cancer; Hormone Receptor Negative Breast Carcinoma; Triple Negative Breast Cancer

Keywords

biomarker directed therapies; biomarker stratified trial

Outcome Measures

Primary Outcomes (1)

• Intra-Individual Progression-Free Survival (PFS)

  Progression-Free Survival (PFS) is defined as the time from initiation of study therapy until documented disease progression per Response Evaluation Criteria In Solid Tumors Criteria (RECIST) v1.1 or death from any cause, whichever occurs first. For intra-individual comparisons across successive therapy lines, a PFS ratio will be calculated by dividing the PFS of the current line (nth line, PFSₙ) by the PFS of the preceding line ((n-1)th line, PFSn-1). This allows each patient to serve as their own control, reducing between-patient variability and normalizing for the expected decline in PFS with later lines. RECIST v1.1 defines Complete Response (CR) as disappearance of all target lesions, Partial Response (PR) as ≥30% decrease, Stable Disease (SD) as insufficient change for PR or PD, and Progressive Disease (PD) as ≥20% increase, measurable growth in non-target lesions, or new lesions.

  Up to 5 years

Secondary Outcomes (12)

• Progression free survival (PFS) - Between-Arm Evaluation

  Up to 3 months

• Tissue- and blood-based biomarkers on response rate

  Up to 3 months

• Overall survival (OS)

  Up to 12 months

• Objective response rate (ORR)

  Up to 3 months

• Duration of response (DoR)

  Up to 12 months

Study Arms (6)

Cohort 1 Arm A

EXPERIMENTAL

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.

Drug: SERD* + abemaciclib

Cohort 1- Arm B

EXPERIMENTAL

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.

Drug: SERD* + everolimus

Cohort 2 Arm A

EXPERIMENTAL

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.

Drug: SERD* + abemaciclib

Cohort 2 Arm B

EXPERIMENTAL

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.

Drug: SERD* + everolimus or capecitabine

Cohort 3

ACTIVE COMPARATOR

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.

Drug: SOC

Cohort 4

EXPERIMENTAL

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.

Drug: Antiandrogen

Interventions

SERD* + abemaciclib DRUG

Investigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy.

Cohort 1 Arm A; Cohort 2 Arm A

SERD* + everolimus DRUG

Investigators choice Selective Estrogen Receptor Degrader + everolimus therapy.

Cohort 1- Arm B

SOC DRUG

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

Cohort 3

SERD* + everolimus or capecitabine DRUG

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

Cohort 2 Arm B

Antiandrogen DRUG

Antiandrogen therapy

Cohort 4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Advanced Research Projects Agency for Health (ARPA-H): collaborator
• Translational Breast Cancer Research Consortium: collaborator
• UNC Lineberger Comprehensive Cancer Center: lead
• Breast Cancer Research Foundation: collaborator

Study Sites (2)

Mayo Clinic

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

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

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

RECRUITING

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

abemaciclib; Everolimus; Capecitabine; Androgen Antagonists

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Hormone Antagonists; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Lisa A Carey, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

• Eric Winer, MD

  Yale University

  STUDY CHAIR

Central Study Contacts

Emily L Schworer

CONTACT

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

Ana Gallegos

CONTACT

ana_gallegos@med.unc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients are stratified according to tumor marker profiles and receive corresponding treatment regimens.

Study Record Dates

• First Submitted: January 12, 2026
• First Posted: January 14, 2026
• Study Start: February 16, 2026
• Primary Completion (Estimated): June 2, 2031
• Study Completion (Estimated): June 2, 2031
• Last Updated: May 20, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)