Biology Guided Therapy Recommendations for Treatment Determination of Hormone Receptor-Positive Advanced, Unresectable or Metastatic Breast Cancer, ENDORSE Trial

Pilot Study: Evaluation of Novel Data-Driven Outcomes Via Response-Guided Systems Medicine in Hormone Receptor-Positive Advanced Breast Cancer (ENDORSE)

This clinical trial tests the feasibility and utility of a biology guided therapy recommendations report to aid in determining treatment of hormone receptor positive breast cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced), that cannot be removed by surgery (unresectable) or that has spread from where it first started (primary site) to other places in the body (metastatic). The biology guided therapy recommendations report is developed from testing a patients tumor tissue when they have progression to see what medications may work best and what medications the cancer may be resistant to based on their tumor biology. Patients and their doctor then receive that report with the suggested treatments. Receiving a biology guided therapy recommendations report may be a feasible and useable way to aid in treatment determination for hormone receptor positive advanced, unresectable or metastatic breast cancer.

Study Overview

• Status: Not yet recruiting
• Conditions: Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Metastatic Hormone Receptor-Positive Breast Carcinoma; Unresectable Hormone Receptor-Positive Breast Carcinoma; Advanced Hormone Receptor-Positive Breast Carcinoma
• Intervention / Treatment: Procedure: Magnetic Resonance Imaging; Procedure: Biospecimen Collection; Procedure: Positron Emission Tomography; Procedure: Computed Tomography; Other: Electronic Health Record Review; Procedure: Bone Scan; Procedure: Biopsy Procedure; Other: Treatment Planning; Other: Treatment Regimen

Detailed Description

PRIMARY OBJECTIVE:

I. To assess the feasibility and utility of using a systems medicine approach to evaluate tumor tissue from patients with hormone receptor-positive HER2-negative unresectable metastatic breast cancer after progression on first line therapy to both predict estrogen dependence and aid in selection of effective standard of care therapy.

SECONDARY OBJECTIVES:

I. To determine the accrual rate (AR). II. To measure the clinical benefit rate (CBR). III. To compare progression free survival (PFS) based on concordance with recommended treatment.

IV. To determine the duration of response (DoR). V. To measure the therapy acceptance rate (TAR).

EXPLORATORY OBJECTIVES:

I. To obtain additional genomic, epigenomic, and transcriptomic data on resistance mechanisms that informs future validation studies, artificial intelligence (AI) model-selected next line of therapy selection with anticipated highest efficacy amongst available options, and advanced AI model development.

II. To assess obstacles to enrollment and pitfalls of the study design to guide future studies.

OUTLINE:

Patients have their tumor tissue analyzed. Their physician receives a report based on their tumor biology consisting of their predicted ongoing response to endocrine therapy, predicted ongoing response to endocrine therapy plus PIK3CA mutation or ESR1 mutation or HER2 mutation or mTOR sensitivity/resistance. The report includes treatment recommendations and the results of the specific tests completed on the tumor tissue. Physicians then determine a treatment regimen for the patient that may or may not include the treatment recommended in the report. Patients undergo blood sample collection and computed tomography (CT) scan or magnetic resonance imaging (MRI) and/or bone scan and/or positron emission tomography (PET) scan throughout the study. Patients may undergo tumor biopsy during screening and may optionally undergo at progression.

After completion of study intervention, patients are followed every 3 months until disease progression.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Medical Center
      • Principal Investigator: Irene M. Kang
      • Contact: Irene M. Kang; Phone Number: 844-756-2047; Email: ikang@coh.org
    • Irvine, California, United States, 92618
      • City of Hope at Irvine Lennar
      • Principal Investigator: Irene M. Kang
      • Contact: Irene M. Kang; Phone Number: 844-756-2047; Email: ikang@coh.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participant must speak English

• Documented informed consent of the participant and/or legally authorized representative.

  • Assent, when appropriate, will be obtained per institutional guidelines

• Agreement to allow the use of archival tissue from diagnostic tumor biopsies

  • If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Patients must have histologically confirmed, unresectable or metastatic hormone receptor positive, HER2 breast cancer. Hormone receptor positive is defined as estrogen receptor >= 10% and/or progesterone receptor >= 10%. Her2 negative per American Society of Clinical Oncology/College of American Pathologists (ASCO-CAP) guidelines

• Patient must have disease progression during or after prior endocrine therapy meeting one of the following criteria:

  • Disease progression on 1st line endocrine therapy for advanced/metastatic breast cancer.
  • Disease progression on or within 2 years of completion of treatment with a CDK4/6i in the adjuvant setting for early- stage breast cancer
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Patient must have at least one lesion amenable to percutaneous core
• Clinically appropriate for biopsy

Exclusion Criteria:

• Prior treatment in the metastatic setting with capecitabine, phosphoinositide 3 kinase (PI3K) inhibitor, mechanistic target of rapamycin (mTOR) inhibitor, protein kinase B (Akt) inhibitor, selective estrogen receptor degrader (SERD), or HER2-targeted therapy, including neratinib
• Known or untreated, or active, brain or leptomeningeal metastases that are deemed inappropriate to pursue therapy guided by systems medicine approach. Enrolled patients may receive radiation or other loco regional therapy prior to initiating systemic therapy on study. History of malignancies other than adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, or other solid tumors not requiring active therapy
• Life expectancy < 1 year
• Pregnant or breastfeeding
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (Biology guided therapy report); Patients have their tumor tissue analyzed. Their physician receives a report based on their tumor biology consisting of their predicted ongoing response to endocrine therapy, predicted ongoing response to endocrine therapy plus PIK3CA mutation or ESR1 mutation or HER2 mutation or mTOR sensitivity/resistance. The report includes treatment recommendations and the results of the specific tests completed on the tumor tissue. Physicians then determine a treatment regimen for the patient that may or may not include the treatment recommended in the report. Patients undergo blood sample collection and CT scan or MRI and/or bone scan and/or PET scan throughout the study. Patients may undergo tumor biopsy during screening and may optionally undergo at progression.

Procedure: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI; Procedure: Biospecimen Collection; Undergo blood sample collection; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Procedure: Positron Emission Tomography; Undergo PET scan; Other Names: Medical Imaging, Positron Emission Tomography; PET; PET Scan; Positron Emission Tomography Scan; Positron-Emission Tomography; PT; Positron emission tomography (procedure); Procedure: Computed Tomography; Undergo CT scan; Other Names: CT; CAT; CAT Scan; Computed Axial Tomography; Computerized Axial Tomography; Computerized Tomography; CT Scan; tomography; Computerized axial tomography (procedure); Computerized Tomography (CT) scan; Diagnostic CAT Scan; Diagnostic CAT Scan Service Type; Other: Electronic Health Record Review; Ancillary studies; Procedure: Bone Scan; Undergo bone scan; Other Names: Bone Scintigraphy; Procedure: Biopsy Procedure; Undergo tumor biopsy; Other Names: Bx; BIOPSY_TYPE; Biopsy; Other: Treatment Planning; Receive tumor biology report with predicted ongoing response; Other: Treatment Regimen; Receive treatment recommendations; Other Names: Regimen; regimen or line of therapy; Regimen/Treatment Period/Vaccination Regimen; regimen_or_line_of_therapy; Treatment Protocol; Treatment Schedule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Turnaround time (feasibility)	Report consists of an Evaluation of Novel Data-driven Outcomes via Response-guided Systems Medicine in Hormone Receptor-positive Advanced Breast Cancer (ENDORSE) signature score, MTOR signature score and status of other Food and Drug Administration approved biomarkers, including ESR1 mutations, PIK3CA mutations and HER2 mutation/expression). The turn-around time will be summarized by the range, mean, median, and standard deviation.	Up to 30 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Accrual rate	Defined as is the number of patients enrolled over the period of a month.	Up to 1 year
Clinical benefit rate	Will be summarized as the percentage of patients with complete response (CR), partial response (PR), or at least stable disease (SD) at 6 months.	At 6 months
Median progression free survival		From study registration to progression, symptomatic deterioration, or death due to any cause, up to 1 year
Duration of overall response		From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, up to 1 year
Therapy acceptance rate	Defined as the proportion of cases in which the recommended therapy by the study was the same as what was recommended by the physician.	Up to 1 year

Collaborators and Investigators

• Sponsor: City of Hope Medical Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Irene M Kang, City of Hope Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): December 19, 2026
• Primary Completion (Estimated): December 2, 2027
• Study Completion (Estimated): December 2, 2027

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Health Care Quality, Access, and Evaluation; Investigative Techniques; Therapeutics; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Surgical Procedures, Operative; Cytological Techniques; Cytodiagnosis; Health Care Evaluation Mechanisms; Quality of Health Care; Diagnostic Techniques, Surgical; Chemistry Techniques, Analytical; Spectrum Analysis; Epidemiologic Study Characteristics; Biopsy; Specimen Handling; Magnetic Resonance Spectroscopy; Clinical Protocols
• Other Study ID Numbers: 24121 (Other Identifier: City of Hope Comprehensive Cancer Center); P30CA033572 (U.S. NIH Grant/Contract); NCI-2026-02741 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No