Comparing Selumetinib and Olaparib to Selumetinib Alone for Ovarian and Endometrial Cancers with RAS Pathway Mutations (EAY191-N4, A ComboMATCH Treatment Trial)

04/12/2023

EAY191-N4 (ComboMATCH): A
Randomized Trial of Selumetinib and Olaparib or Selumetinib Alone in Patients
with Recurrent or Persistent RAS Pathway Mutant Ovarian and Endometrial Cancers

The EAY191-N4 clinical study,  part of the

ComboMATCH precision medicine initiative, is open for women who have recurrent or  persistent ovarian and endometrial with a RAS pathway mutation, including  activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, and MEK2, or in activating 
mutations in NF1. The trial will be comparing the combination of the MEK  inhibitor Selumetinib and the PARP inhibitor Olaparib to Selumetinib alone for 
this patient population. The study will be occurring in two different cohorts.  Cohort 1 will consist of patients with ovarian cancer and Cohort 2 will include 
patients with endometrial cancer.

“Ovarian cancer is the
national leader of gynecologic cancer mortality in women in the United States
and endometrial cancer is the fourth most common malignancy in women globally.
Although these diseases impact such a large scale of women, it has been difficult
to find an effective, single-agent treatment to improve outcomes in these
populations,” stated Shannon N. Westin, MD, MPH, of the MD Anderson Cancer
Center and the Principal Investigator of the EAY191-N4 trial. “Combination 
therapies are being considered based on ovarian and endometrial genomic factors  and preclinical data has suggested that the combination PARP and MEK inhibitors  could improve response and survival outcomes for these women with RAS pathway  mutations.”

EAY191-N4 will enroll patients
with  ovarian and endometrial cancers who have RAS pathway mutations, however  patients cannot have prior treatment with MEK inhibitors, PARP inhibitors with  disease progression, or myelodysplastic syndrome or acute myeloid leukemia.  Patients will be separated into cohorts based on ovarian versus endometrial  cancer. Patients in the ovarian cancer cohort will be stratified by low grade 
serous ovarian cancer versus other ovarian cancers prior to their randomization  to Selumetinib and Olaparib or Selumetinib alone treatment arms. Patients in  the endometrial cancer cohort will be stratified by endometrioid cancer versus
other endometrial cancer prior to their randomization to Selumetinib and 
Olaparib or Selumetinib alone treatment arms. For each group, patients who are
treated with Selumetinib alone are able to cross over to the Selumetinib and 
Olaparib treatment if their disease progresses.

The primary objectives of the 
EAY191-N4 clinical study is to compare progression free survival between 
treatment arms for patients with RAS mutant ovarian and endometrial cancers.  Secondary objectives include determining the safety, comparing objective  response rates, and reporting the duration of response between treatment arms.
The study also involves the translational objective of assessing the 
association of baseline genomic and transcriptomic status with response and  resistance to therapy.

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

.