Treating Advanced Endometrial or Ovarian Cancer with Targeted Therapies (ComboMATCH)

About the Study

This clinical trial is testing whether two targeted cancer drugs taken together work better than one drug alone for treating advanced ovarian or endometrial cancer that has come back or did not respond to prior treatment. To be eligible, the cancer must test positive for a biomarker known as a RAS mutation. One of the drugs, selumetinib (Koselugo) is currently used to shrink tumors caused by a rare condition called neurofibromatosis (NF1). The second drug, olaparib (Lynparza) is a type of cancer drug known as a PARP inhibitor. 

What the Study Involves

Participants must first join and consent to a study called the ComboMATCH Master Registration Trial EAY191. As part of this study, participants' tumors will be checked for certain biomarkers. 

Participants may be eligible if their tumor has a biomarker known as a KRAS pathway mutation. 

Eligible participants will be randomly selected for one of two groups:

• Group 1 participants will receive selumetinib alone. If cancer worsens on selumetinib alone, some participants may be able to switch to the combination treatment.
• Group 2 participants will receive selumetinib plus olaparib.

Both drugs are oral medications (taken by mouth). 

Participants in both groups will continue taking the study drugs as long as their cancer does not get worse and side effects remain manageable. During the study, participants will have regular doctor visits, imaging tests (such as CT scans), and blood tests so the study team can monitor side effects and see how well the treatment is working.

Participants will be followed with laboratory tests for up to 5 years after stopping treatment. 

Participants with all of the following may be eligible to participate:

• Advanced endometrial or ovarian cancer that has come back or has not responded to first-line or later treatment. There is no upper limit to the number of prior treatments received.
• Must have cancer in a location that can be safely sampled for biomarker testing. If it is not safe to take a biopsy, people may be able to participate if they have tissue available from a previous biopsy taken within the last 12 months.
• Must test positive for a KRAS pathway mutation in their tumor.
• Must be at least 4 weeks since last prior treatment. Any side effects from prior treatments must be managed. 
• For endometrial cancer, participants must have received or been offered an immunotherapy drug (alone or in combination with lenvatinib) unless there are reasons why they could not safely receive either drug. 
• For ovarian cancer, participants must no longer be able to receive platinum chemotherapy. 
• Must have adequate heart, kidney, liver, and bone marrow function.
• Any infections (such as HIV or hepatitis) must be treated and under control.

See full inclusion list here. 

People may not participate if any of the following apply:

• Previously received any drugs know as MEK inhibitors.
• Previously received and cancer got worse while receiving a PARP inhibitor.
• Receiving certain medications or supplements that may interact with treatment medications.
• Have conditions of the eyes, including uncontrolled glaucoma, history of retinal detachment or other retinal conditions.    

See full exclusion list here.