This phase II ComboMATCH treatment trial compares selumetinib plus olaparib to selumetinib alone in women with endometrial or ovarian (fallopian tube and primary peritoneal) cancer that has come back (recurrent) or that remains despite treatment (persistent) and harbors a mutation in the RAS pathway. Selumetinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Olaparib is an inhibitor of PARP, an enzyme that helps repair deoxyribonucleic acid (DNA) when it becomes damaged. Blocking PARP may help keep tumor cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. The addition of olaparib to selumetinib could increase the percentage of tumors that shrink as well as lengthen the time that the tumors remain stable (without progression) as compared to selumetinib alone.
Patient must have enrolled onto EAY191 and must have been given a treatment assignment to ComboMATCH to EAY191-N4 based on the presence of an actionable mutation as defined in EAY191
Patients must be enrolled on the ComboMATCH Master Registration Trial EAY191
Patients must have RAS pathway mutations as determined by the ComboMATCH screening assessment
Cohort 1: Patients with histologically confirmed RAS pathway mutant ovarian, primary peritoneal, or fallopian tube ("ovarian") cancer (activating mutations in KRAS, NRAS, HRAS, BRAF, MEK1, MEK2, or inactivating mutations in NF1)
Patients who have received any MEK inhibitors
Patients who have progressed while receiving a PARP inhibitor
Patients who have received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration
Patients who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > grade 1) with the exception of alopecia
National Cancer Institute (NCI)
Lead sponsor
NRG Oncology
Collaborator