KRAS is a commonly mutated gene across solid tumors, thus makes it a potential target for anti-tumor drugs. Recently, some developing drugs showed potential in treating the KRAS G12C mutant. However, there is no available targeted therapy for patients harbored other KRAS mutations. In a phase 1 study, CH5126766 (an RAF-MEK inhibitor) demonstrated its anti-tumor activity in several RAS/RAF-mutant solid tumors. This trial enrolled a total of 29 patients in the basket dose-expansion cohort, and 26 were evaluable for response. Among them, 10 were non-small-cell lung cancer, 5 were gynecological malignancy, 4 were colorectal cancer, 1 was melanoma, and 6 were multiple myeloma. Seven of 26 (26.9%) had an objective response. The ORR for NSCLC, gynecological malignancy, and CRC were 30%, 60%, and 0%. The above results suggested that CH5126766 is highly potent for treating NSCLCs and gynecological cancers harboring a KRAS/BRAF mutation. However, the use of CH5126766 as a monotherapy or in a combination regimen needs to be further evaluated.
Lancet Oncol. 2020 Nov;21(11):1478-1488.