AstraZeneca (AZ) has started late-stage clinical trials of its MEK inhibitor selumetinib in advanced non-small-cell lung cancer (NSCLC).
The drug is being investigated with docetaxel as a second-line treatment for NSCLC tumours that are KRAS mutation positive, a sub-type of lung cancer associated with poor prognosis and limited treatment options.
The SELECT-1 trial is the largest prospective study ever conducted in this patient population and AZ hopes to show the combination is better than chemotherapy alone.
It will enrol more than 630 patients who will receive either a twice-daily 75mg dose of selumetinib or placebo in combination with docetaxel, administered intravenously on a 21-day cycle.
Antoine Yver, head of oncology in AZ’s Global Medicines Development unit, said: “To our knowledge, SELECT-1 will be the first phase III study to investigate whether a MEK inhibitor in combination with chemotherapy is superior to chemotherapy alone in KRAS mutation positive advanced or metastatic non-small cell lung cancer.
“This is an area of pressing clinical need, and our decision to progress selumetinib was based on phase II results, which showed promising clinical activity in this group of patients.”
Selumetinib was moved into phase III trials after positive phase II results showing selumetinib plus docetaxel increased progression-free survival by 3.2 months compared to docetaxel alone in KRAS-mutation positive NSCLC.
Mitogen-activated protein kinase, or MEK, is part of the MAPK pathway, which is frequently activated in cancer and is elevated in many different solid tumour types, including those featuring the KRAS mutation.
The KRAS mutation is present in 20 to 30 per cent of NSCLC tumours and AZ has partnered with Roche Molecular Systems to develop a KRAS diagnostic device to identify patients most likely to benefit from selumetinib.
The drug is also being studied across a range of other MEK-dependent cancers. AZ started a phase II study of selumetinib in thyroid cancer in August and will later this year begin a phase II study in patients with the rare cancer metastatic uveal melanoma.