April 12 2023
EAY191-N2 (ComboMATCH): 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
The EAY191-N2 clinical study, part of the ComboMATCH precision medicine initiative, is open for patients who have hormone receptor-positive (HR+) breast cancer with NF1 Nonsense or Frameshift mutation. Patients will be enrolled into two different cohorts. Cohort 1 is testing the combination of fulvestrant and binimetinib in HR+ patients who have never received fulvestrant (fulvestrant-naïve). Cohort 2 is assessing the addition of binimetinib to fulvestrant for patients who have previously received fulvestrant (fulvestrant-exposed) and their disease progressed.
“NF1 mutations are rare in primary estrogen receptor-positive (ER+) breast cancer, however, rates NF1 mutation frequency is much higher in patients with metastatic ER+ breast cancer. The agent fulvestrant has exhibited initial efficacy in NF1 lost ER+ breast cancer, however, typically results in eventual resistance from the activation of the Ras-Raf-MEK-ERK pathway, which can be blocked by addition of binimetinib,” stated Bora Lim, MD, of the Baylor College of Medicine and the Principal Investigator of the EAY191-N2 trial.
“EAY191-N2 hopes that adding the MEK inhibitor, binimetinib, to fulvestrant can help improve progression-free survival for patients who are fulvestrant-naïve, and can improve the overall response rate for patients that are previously fulvestrant-exposed,” added Roisin O’Cearbhaill, MD, of the Memorial Sloan Kettering Cancer Center, the NRG Oncology Developmental Therapeutics Committee Chair, and Co-Principal Investigator of the EAY191-N2 trial.
In addition to the primary objectives of improving progression free survival (Cohort 1) and comparing overall response rates (Cohort 2), EAY191-N2 also includes the secondary objectives of clinical benefit rate, safety and toxicity, and overall survival in both cohorts. Exploratory biomarker objective include the analysis of the cfDNA and RNAseq at progression, the detection of novel biomarkers, loss of NF1, and the variant allele frequency of mutant NF1.
This clinical trial is currently active and accruing patients. For individuals interested in joining this trial, the first step is to enroll in the ComboMATCH Patient Registration Trial (EAY191) through their oncologist.
Protocol documents and materials are located on the CTSU website.