A plain language summary of POLARIS: a study to look at different doses of encorafenib plus binimetinib for people with BRAF V600-mutant melanoma with brain metastasis.

What is this summary about?People with a type of melanoma called advanced or metastatic BRAF V600- mutant melanoma, with a change in the BRAF gene, that has spread to the brain have poor outcomes.Current treatments include encorafenib (BRAFTOVI®) and binimetinib (MEKTOVI®). The POLARIS clinical study looked at whether increasing the encorafenib dose would make treatment more effective, with similar side effects, in these patients.The first part of the study, known as the safety lead-in, looked at the side effects of a high dose of encorafenib together with binimetinib. This was followed by a phase 2 part to look at 2 different doses of the encorafenib plus binimetinib treatment. Participants took the standard dose of encorafenib plus binimetinib. Those who tolerated the standard dose could then take a higher dose of encorafenib.What were the results?POLARIS included 13 participants: 10 in the safety lead-in and 3 in the phase 2 part. In the safety lead-in, many participants could not tolerate the high dose of encorafenib plus binimetinib. After treatment, for 1 participant, all signs of cancer in the brain had disappeared and for 5 participants, the amount of cancer in the brain had decreased. Because many participants had too many side effects with the high dose, the standard dose was chosen for the phase 2 part.In the phase 2 part, participants who tolerated the standard dose of encorafenib plus binimetinib could then take a higher dose (increased dose). Of the 3 participants, 1 continued at the standard dose and 2 took the increased dose.The proportion of participants with brain metastases who had a smaller tumor size or complete disappearance of the tumors after treatment with encorafenib plus binimetinib was similar in the safety lead-in and phase 2 parts of the study.What do the results mean?This was the first study of high-dose encorafenib plus binimetinib in people with BRAF V600-mutant melanoma and brain metastasis. Despite the small number of participants, the POLARIS study confirmed that the standard dose of encorafenib plus binimetinib worked as well as the high dose to decrease the amount of cancer in the brain and had fewer side effects.[Box: see text].