BRAF and melanoma: For BRAF-wild-type (BRAFwt) melanoma, targeted therapies have not been proven to provide benefit in the metastatic setting, but MEK inhibition has been demonstrated to synergize with anti-PD-1 in several preclinical models of cancer20; this approach showed promise in a Phase Ib clinical trial, although a subsequent Phase II trial (reported after our study was activated) did not substantiate this21,22.