What is your preferred first-line treatment for metastatic melanoma in a patient with a class 2/non-V600 BRAF mutation?

Class II BRAF mutations have intermediate kinase activity and are much less likely than V600E or V600K mutations to respond to traditional BRAF+MEK inhibitor therapy. Targeted therapy should not be used as a front-line therapy in these patients. Immunotherapy (and immunotherapy-based front-line clin...

Class II BRAF mutations have an intermediate level of constitutional kinase activation through RAS dependent dimers and the current FDA approved BRAF inhibitors are monomer selective. There are some dimer selective agents currently under investigation such as αC-IN inhibitor and RAF inhibitor PLX839...

My preferred first-line treatment in this setting is combination checkpoint inhibitor therapy with ipilimumab + nivolumab. As @Dr. First Last and @Dr. First Last have noted, Class II BRAF mutations are less likely to respond to traditional BRAF+MEK targeted therapy.

In addition, I prefer this regime...

The answers already given are excellent. I would only agree that front line immunotherapy, either standard or on a trial, is likely the best choice. If there is a clinical trial with a targeted agent that offers the possibility of similar long term benefits, that would also be an excellent first cho...