Selumetinib is a potent inhibitor of MEK1/2 that directly targets the MEK/ERK pathway, which is constitutively activated in many cancers and contributes to resistance. Mutations in genes upstream of MEK like KRAS and BRAF are common in cancers like melanoma, thyroid, colon, lung and activate this pathway. Preclinical studies show selumetinib has antitumor activity in NSCLC models, particularly those with KRAS/BRAF mutations. Ongoing clinical trials are investigating selumetinib alone or in combination with other drugs as a treatment for advanced NSCLC.

4. A Phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of AZD6244 (hyd-sulfate) in combination with docetaxel, compared with docetaxel alone, in second-line patients with KRAS mutation-positive local advanced or metastatic non s mall-cell lung cancer (Stage IIIB-IV). Stage IIIB-IV NSCLC pts with confirmed KRAS mutation, progressing after, or intolerant to, I-line chemotherapy Primary Endpoint: PFS; Secondary endpoints: OS, ORR, response duration, tumor shrinkage at 12 weeks, PFS/OS rate at 6 mo, safety and tolerability, pharmacokinetics Projected accrual: 80 pts Currently ongoing in: Belgium, Brazil, Canada, Czech Republic, Denmark, France, Hungary, Italy, Mexico, Peru, Spain, United States Available at: www.clinicaltrials.gov . NCT00890825 . http://www.clinicaltrials.gov/ct2/show/NCT00890825?term=NCT00890825&rank=1