trametinib + azacitidine

This investigational combination therapy consists of trametinib, an orally bioavailable MEK1/2 inhibitor, and azacitidine, a hypomethylating agent, for the treatment of newly diagnosed juvenile myelomonocytic leukemia (JMML). Trametinib (brand name Mekinist) is a highly selective allosteric inhibitor of the Ras/MAPK signaling pathway, which is frequently mutated in JMML (e.g., NF1, NRAS, KRAS). Azacitidine acts as a DNA methyltransferase inhibitor, addressing the aberrant DNA methylation patterns characteristic of high-risk JMML. The therapy is being evaluated in the Phase I/II TRAZA trial (T2020-004) conducted by the Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) Consortium. The study utilizes a risk-stratified approach: lower-risk patients receive the trametinib and azacitidine doublet for up to 12 cycles, while high-risk patients receive the combination alongside fludarabine and cytarabine chemotherapy as a bridge to hematopoietic stem cell transplant.

Brand names

Mekinist

Other names

trametinib-Therapeutic Advances in Childhood Leukemia Consortium-juvenile myelomonocytic leukemiatrametinib and azacitidine