---
title: Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies
nct_id: NCT07340541
overall_status: RECRUITING
phase: PHASE2
sponsor: UNC Lineberger Comprehensive Cancer Center
study_type: INTERVENTIONAL
primary_condition: Breast Cancer
countries: United States
canonical_url: "https://parkinsonspathways.com/agent/trials/NCT07340541.md"
clinicaltrials_gov: "https://clinicaltrials.gov/study/NCT07340541"
ct_last_update_post_date: 2026-04-13
last_seen_at: "2026-05-12T06:20:43.685Z"
source: ClinicalTrials.gov (mirrored, no enrichment)
---
# Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies

**Official Title:** TBCRC Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies (EVOLVE-BDT)

**NCT ID:** [NCT07340541](https://clinicaltrials.gov/study/NCT07340541)

## Key Facts

- **Status:** RECRUITING
- **Phase:** PHASE2
- **Study Type:** INTERVENTIONAL
- **Target Enrollment:** 700
- **Lead Sponsor:** UNC Lineberger Comprehensive Cancer Center
- **Collaborators:** Advanced Research Projects Agency for Health (ARPA-H), Breast Cancer Research Foundation, Translational Breast Cancer Research Consortium
- **Conditions:** Breast Cancer, Metastatic Breast Cancer, Triple Negative Breast Cancer, Estrogen-receptor-positive Breast Cancer, Hormone Receptor Negative Breast Carcinoma
- **Start Date:** 2026-02-16
- **Completion Date:** 2031-06-02
- **CT.gov Last Update:** 2026-04-13

## 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.

## Detailed Description

The platform design makes it easy to assess multiple targeted therapies at the same time, focusing on patient groups identified by specific biomarkers. Patients who experience disease progression may be reassigned to additional eligible sub trials evaluating alternative therapeutic options. The primary endpoint for each arm is progression-free survival (PFS). This adaptive framework enables continuous learning and rapid translation of biomarker discoveries into therapeutic evaluation, promoting an agile and data-driven approach to treatment optimization in advanced breast cancer.

Beyond ER and HER2, there are few biomarkers to drive treatment decisions in metastatic and primary breast cancer, leaving a gap in effective treatments for other subtypes. To address this, triple-negative (TNBC) is pioneering an adaptive, evolutionary trial focusing on women with metastatic breast cancer (MBC) in the second-line (2L) setting. The adaptive trial infrastructure is designed to serve as an integrated parent study, enabling coordinated acquisition of clinical and translational data, as well as training and testing activities. Within this framework, individual biomarker-driven sub-trials (based on biomarker development) can be created and conducted.

Eligible participants include patients with ER+/HER2- or triple-negative (TNBC) metastatic breast cancer (MBC) who have progressed on first line (1L) therapy but have not yet initiated second-line (2L) treatment. HER2+ patients will be excluded due to the availability of established effective therapies.

This Sub Protocol #1 will enroll subjects based on biomarker subtype. Participants will receive a 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. In order to participate in Sub Protocol #1 subjects must have consented to the Parent protocol.

## Eligibility

- **Minimum age:** 18 Years
- **Sex:** ALL
- **Healthy Volunteers:** No

```
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
```

## Arms

- **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.
- **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.
- **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.
- **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.
- **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.
- **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.

## Interventions

- **SERD* + abemaciclib** (DRUG) — Investigators choice Selective Estrogen Receptor Degrader + abemaciclib therapy.
- **SERD* + everolimus** (DRUG) — Investigators choice Selective Estrogen Receptor Degrader + everolimus therapy.
- **SERD* + everolimus or capecitabine** (DRUG) — Investigators choice Selective Estrogen Receptor Degrader + everolimus or capecitabine therapy.
- **SOC** (DRUG) — standard-of-care (SOC) chemotherapy in breast cancer
- **Antiandrogen** (DRUG) — Antiandrogen therapy

## Primary Outcomes

- **Intra-Individual Progression-Free Survival (PFS)** _(time frame: Up to 5 years)_ — 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.

## Secondary Outcomes

- **Progression free survival (PFS) - Between-Arm Evaluation** _(time frame: Up to 3 months)_
- **Tissue- and blood-based biomarkers on response rate** _(time frame: Up to 3 months)_
- **Overall survival (OS)** _(time frame: Up to 12 months)_
- **Objective response rate (ORR)** _(time frame: Up to 3 months)_
- **Duration of response (DoR)** _(time frame: Up to 12 months)_
- **Clinical benefit rate (CBR)** _(time frame: Up to 12 months)_
- **Grade 2 or above Adverse Events per NCI Common Terminology Criteria for Adverse Events (CTCAE)** _(time frame: Up to 12 months)_
- **Changes in circulating tumor DNA (ctDNA) levels** _(time frame: Up to 12 months)_
- **Changes in transcriptomic data - tissue** _(time frame: Up to 12 months)_
- **Changes in transcriptomic data - blood** _(time frame: Up to 12 months)_
- **Changes in Circulating tumor DNA (ctDNA) and tumor response relation** _(time frame: Up to 12 months)_
- **Progression free survival (PFS) -Within Arm Evaluation** _(time frame: Up to 5 years)_

## Locations (1)

- Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill, Chapel Hill, North Carolina, United States — _RECRUITING_

## Recent Field Changes (last 30 days)

- `status.overallStatus` — added _(2026-05-12)_
- `status.primaryCompletionDate` — added _(2026-05-12)_
- `status.completionDate` — added _(2026-05-12)_
- `status.lastUpdatePostDate` — added _(2026-05-12)_
- `design.phases` — added _(2026-05-12)_
- `design.enrollmentCount` — added _(2026-05-12)_
- `eligibility.criteria` — added _(2026-05-12)_
- `eligibility.minAge` — added _(2026-05-12)_
- `eligibility.sex` — added _(2026-05-12)_
- `outcomes.primary` — added _(2026-05-12)_
- `outcomes.secondary` — added _(2026-05-12)_
- `armsInterventions.arms` — added _(2026-05-12)_
- `armsInterventions.interventions` — added _(2026-05-12)_
- `sponsor.lead` — added _(2026-05-12)_
- `sponsor.collaborators` — added _(2026-05-12)_
- `results.hasResults` — added _(2026-05-12)_
- `locations.lineberger comprehensive cancer center at university of north carolina - chapel hill|chapel hill|north carolina|united states` — added _(2026-05-12)_

---

*Canonical: https://parkinsonspathways.com/agent/trials/NCT07340541.md*  
*Source data (authoritative): https://clinicaltrials.gov/study/NCT07340541*  
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