Phase II Trial of Fulvestrant and Binimetinib in Patients with Hormone Receptor-Positive Metastatic Breast Cancer with a Frameshift or Nonsense Mutation or Genomic Deletion in NF1

Protocol: ECOG – EAY191-N2

SCHEMA EAY191-N2

Please Note: Below is a list of brief eligibility requirements, please contact GHCI Research Department at (810) 762-8181, (810) 762-8079 or (810) 762-8038, to discuss full eligibility requirements.

Eligibility:

1. The patient must be enrolled on the ComboMATCH Master Registration Trial EAY191.
2. Patients must have disease that can be safely biopsied and agree to a pre-treatment biopsy or, if disease cannot be safely biopsied, have archival tissue available from within 12
   months prior to the date of registration on the ComboMATCH Registration Trial (EAY191).
3. Age ≥ 18.
4. ECOG performance status 0-2 within 14 days prior to registration.
5. Histologically or cytologically confirmed invasive breast carcinoma.
6. Confirmed metastatic disease by either imaging or tissue diagnosis.
7. Measurable disease.
8. Patients must have NF1 Nonsense or Frameshift mutation, or NF1 whole gene deletion detected in tumor as determined by the ComboMATCH screening assessment.
9. The tumor must have been determined to be ER and/or PgR positive assessed by current ASCO/CAP Guideline Recommendations for hormone receptor testing. Patients with
   ≥ 1% ER or PgR staining by IHC are considered positive.
10. The tumor must have been determined to be HER2-negative by current ASCO/CAP guidelines.
11. Prior therapy:
    1. Prior use of CDK4/6i is required
    2. Prior use of fulvestrant regardless of duration.is allowed and will determine treatment assignment.
    3. Up to one line of chemotherapy in metastatic setting is allowed.
12. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the
    investigational regimen are eligible for this trial.