avutometinib + defactinib + letrozole

This combination therapy consists of avutometinib (a dual RAF/MEK clamp), defactinib (a focal adhesion kinase inhibitor), and letrozole (an aromatase inhibitor). It is primarily being investigated by Memorial Sloan Kettering Cancer Center (MSK) as an upfront, chemotherapy-free treatment for patients with low-grade serous ovarian cancer (LGSOC). Avutometinib inhibits the MAPK pathway by blocking both MEK and RAF proteins, while defactinib targets focal adhesion kinase (FAK) to overcome resistance mechanisms often seen with MEK inhibition. Letrozole provides hormonal blockade, which is relevant as LGSOC is frequently estrogen-receptor positive. The triple combination is currently being evaluated in the Phase 2 CHAMELEON study for patients who have not yet received chemotherapy or hormonal therapy.

Brand names

AvmapkiFakzynja

Other names

CHAMELEON regimenavutometinib + defactinib + letrozole combination