BRAF and melanoma: Although we did not measure serum MIC-1 protein, or other relevant biomarker in our study, we can extrapolate from the biomarker results of the phase I solid tumor or multiple myeloma study to suggest that our recommended phase 2 dose of AMG 232 combined with trametinib alone or trametinib plus dabrafenib at 120 mg may not be sufficiently high to yield a biological effect that is significantly higher than the antitumor effect seen with MEK inhibition alone in patients with non-BRAFV600-mutant or with combined BRAF/MEK inhibition in patients with BRAFV600-mutant melanoma.