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Cobimetinib + dexamethasone is an investigational combination regimen consisting of the MEK1/MEK2 inhibitor cobimetinib and the synthetic glucocorticoid dexamethasone. This combination is primarily being evaluated for the treatment of relapsed or refractory multiple myeloma, particularly in patients whose tumors harbor activating mutations in the MAPK pathway (such as KRAS, NRAS, or BRAF mutations). Cobimetinib selectively blocks MEK1 and MEK2 to inhibit downstream ERK phosphorylation and tumor cell proliferation, while dexamethasone provides synergistic anti-myeloma activity through glucocorticoid receptor activation. The regimen has been studied as a targeted lead-in therapy in the genomically-guided MyDRUG platform trial.
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