Testing the Use of the Combination of Selumetinib and Olaparib or Selumetinib Alone Targeted Treatment for RAS Pathway Mutant Recurrent or Persistent Ovarian and Endometrial Cancers, A ComboMATCH Treatment Trial

Required: BRAF activating mutation

Required: HRAS activating mutation

Required: KRAS activating mutation

Required: MAP2K1 activating mutation

Required: MAP2K2 activating mutation

Required: NF1 inactivating mutation

Required: NRAS activating mutation

Must have received: systemic therapy — recurrent or persistent disease

Patients must have progressed after first-line treatment for recurrent or persistent disease

Must have received: immune oncology agent — endometrial cancer

Patients with endometrial cancer must have received or been offered an immune oncology agent (alone or in combination with lenvatinib) unless there are existing contraindications

Cannot have received: MEK inhibitor

Patients who have received any MEK inhibitors

Cannot have received: PARP inhibitor

Patients who have progressed while receiving a PARP inhibitor

Cannot have received: chemotherapy (nitrosoureas, mitomycin C)

Patients who have received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration

Cannot have received: radiotherapy

Patients who have received chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to registration

Cannot have received: systemic anti-cancer treatment

Have received or are receiving an investigational medicinal product (IMP) or other systemic anti-cancer treatment (including chemotherapy, immunotherapy, targeted therapy, biologic therapy, tumor embolization, or monoclonal antibodies) within 4 weeks prior to registration, or within a period during which the IMP or systemic target treatment has not been cleared from the body (e.g., a period of 5 'half-lives'), whichever is longer