AMG 232 + trametinib

AMG 232 + trametinib is a **combination therapy** evaluated in clinical studies primarily for *TP53 wild-type* metastatic melanoma and relapsed/refractory acute myeloid leukemia. AMG 232 is an investigational, oral, selective small molecule that inhibits MDM2, thereby disrupting the MDM2-p53 protein-protein interaction and reactivating p53-dependent tumor suppression. Trametinib is a small molecule inhibitor of MEK1 and MEK2, components of the MAPK signaling pathway, which blocks downstream signaling of cell proliferation and survival in cancers with activated MAPK pathway. Together, this combination is designed to synergistically promote p53-mediated apoptosis and inhibit tumor growth in cancer cells, especially those without TP53 mutations. AMG 232 was developed by Amgen. Trametinib was originally developed by GSK. Primary indications studied include metastatic melanoma (both BRAF-mutant and BRAF-wild type) and relapsed/refractory acute myeloid leukemia, with trials primarily in phase 1 and phase 2 settings.[1][3][5]