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

April 12 2023

EAY191-N4 (ComboMATCH): ARandomized Trial of Selumetinib and Olaparib or Selumetinib Alone in Patientswith 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 thenational leader of gynecologic cancer mortality in women in the United Statesand endometrial cancer is the fourth most common malignancy in women globally.Although these diseases impact such a large scale of women, it has been difficultto find an effective, single-agent treatment to improve outcomes in thesepopulations,” stated Shannon N. Westin, MD, MPH, of the MD Anderson CancerCenter 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 patientswith  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 versusother endometrial cancer prior to their randomization to Selumetinib and Olaparib or Selumetinib alone treatment arms. For each group, patients who aretreated 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 iscurrently active and accruing patients. For individuals interested injoining 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

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