Neu Direction: Testing the Efficacy of Adding HER Inhibition to Standard of Care in Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer | NCT07729046

NCT07729046

Overview

NCT ID: NCT07729046
Lead Sponsor: University of California, San DiegoOTHER
Official Title: Neu Direction: A Single Center Phase II Randomized Clinical Trial to Assess the Efficacy of Adding HER Inhibition to Standard of Care in Patients With Metastatic MLH1-low Endocrine-resistant ER+/HER2- Breast Cancer
Brief Summary: The goal of this clinical trial is to learn if neratinib, an FDA-approved oral pan-HER2/3/4 inhibitor, improves disease control for participants with metastatic endocrine-resistant ER+/HER2-negative breast cancer. Neratinib is already approved for the treatment of HER2-postive breast cancers. The study will also learn about the safety of adding this drug to standard of care treatments. The main questions it aims to answer are:

Does adding neratinib to standard of care systemic therapy improve disease control for patients with metastatic hormone-driven breast cancer that is resistant to endocrine therapy?

What side effects do participants have when adding neratinib to standard of care therapy? Researchers will compare standard of care endocrine therapy regimens with and without neratinib to see if neratinib improves control of treatment-resistant metastatic breast cancer that has continued to progress while eon first line endocrine therapy.

Participants will:

Take standard of care endocrine therapy for metastatic endocrine-resistant breast cancer as determined by their medical oncologist or standard of care therapy with neratinib daily

Visit the clinic every 3 months for checkups, tests and imaging studies

Status and Timeline

Status: Not yet recruiting
Last Update Posted: Jul 27, 2026Actual
Start Date: Jul 2027Estimated
Primary Completion Date: May 2032Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: Female
Accepts Healthy Volunteers?: No
Eligibility Criteria: Inclusion Criteria:

Female over the age of 18 at the time of study enrollment

Not pregnant, planning to become pregnant or breast feeding

Metastatic ER+/HER2- breast cancer that has progressed on 1st line therapy including endocrine therapy +/- CDK4/6 inhibitors

At least one metastatic lesion visible on imaging (including FDG-PET)

At least one metastatic lesion must be biopsied and confirmed ER+ and HER2- by immunohistochemistry within 6 months of study screening (HER2 equivocal disease will be confirmed HER2- by FISH)

Tumors must be MLH1-low defined by <50% tumor cells positive for nuclear MLH1 expression on immunohistochemistry

Standard of care next line endocrine therapy can include any endocrine therapy

Performance status ECOG > 3

Life expectancy > 1 year

Ability to get serial imaging studies

Exclusion Criteria:

History of concurrent use of other HER2-targeted therapy

Concurrent use of other targeted systemic therapy

History of other cancers other than non-melanoma skin cancer

Actionable mutations on tumor genomic sequencing will be ineligible, and those participants encouraged to proceed with the relevant targeted therapy

Participants where there is not at least one imaging apparent lesion that has not been treated with prior targeted therapy (for example palliative radiation or cryoablation)

Contraindications to Neratinib use including allergy or hypersensitivity

Baseline grade 3+ diarrhea

Study Plan

Study Type: Interventional
Phase: Phase 2
Enrollment: 150Estimated
Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Parallel Assignment
Masking: Single

Contacts and Locations

Central Contacts: Asona Lui, MD, PhDContact
ajlui@health.ucsd.edu858-822-4319

Overview

Status and Timeline

Participation Criteria

Study Plan

Contacts and Locations

Similar Studies