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

Conditions

• ER+, HER2-, Metastatic Breast Cancer
• Metastatic Invasive Breast Cancer
• Resistant Breast Cancer

Eligibility Criteria

Sex

FEMALE

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Neratinib + endocrine therapy — DRUG
  Neratinib 120mg daily for 1 week, 160mg daily for 1 week and then 240mg daily thereafter
• Endocrine therapy may include one of the following therapies: letrozole, anastrozole, exemestane, tamoxifen or fulvestrant — DRUG
  Endocrine therapy with out without CDK4/6 inhibitor
• CDK4/6 + Endocrine therapy — DRUG
  Endocrine therapy with or without CDK 4/6 inhibitor

Study Details

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: 1. 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? 2. 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: 1. 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 2. Visit the clinic every 3 months for checkups, tests and imaging studies

Key Dates

First listed

Jul 27, 2026

Start date

Jul 31, 2027

Status verified

Jul 2026

Primary completion

May 31, 2032

Completion

Jun 30, 2035

Study Design

Enrollment

150 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Active Comparator: Standard of Care
  Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor
• Experimental: Stanard of Care + Neratinib
  Standard of Care 2nd or 3rd line endocrine therapy with or without CDK4/6 inhibitor + Neratinib

Primary Outcome Measure

Median Progression-Free Survival [ Time Frame: From enrollment through study completion, an average of 1 year. ]

Central Contacts

• Asona Lui, MD, PhD
  858-822-4319
  [email protected]
• Alyssa Beck, MD
  858-657-7000
  [email protected]

Locations (1)

Find similar trials in La Jolla, CA

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