AstraZeneca has dosed first patient in the phase III clinical programme for selumetinib, an oral, potent, selective MEK inhibitor, being investigated as second-line therapy in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) whose tumours are KRAS mutation-positive.
The SELumetinib Evaluation as Combination Therapy-1 (SELECT-1) study is a randomised, double-blind, placebo-controlled study that will evaluate the safety and efficacy of selumetinib plus docetaxel as a second line therapy in locally advanced or metastatic KRAS mutation-positive NSCLC. The study is designed to evaluate Progression Free Survival (PFS) and Overall Survival (OS). SELECT-1 will be the largest prospective study ever conducted in this patient population, a genetic sub-type of lung cancer associated with poor prognosis and limited treatment options.
The decision to progress selumetinib to phase III studies in NSCLC followed the results from Study 16, a randomised phase II study evaluating the combination of selumetinib with standard of care docetaxel against docetaxel alone in KRAS-mutation positive NSCLC. Study 16 demonstrated a high and durable response rate of 37.2% vs 0% (p<0.0001), translating into a statistically significant improvement in progression free survival (PFS) of 5.3 vs 2.1 months (HR 0.58, p<0.014).
AstraZeneca acquired exclusive worldwide rights to selumetinib from Array BioPharma in 2003.
Antoine Yver, vice president and head of Oncology in AstraZeneca’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.”
The SELECT-1 trial will include 220 centres globally and enroll 634 patients, who will be randomized in a ratio of 1:1 to receive either selumetinib (75mg, orally, twice daily) or matching placebo in combination with docetaxel (intravenously, 75mg / m2, on day one of every 21 day cycle).
Selumetinib is an oral, potent, selective MEK inhibitor, which has been shown to be effective as monotherapy and in combination with standard chemotherapy regimens in phase I and phase II clinical studies across a range of solid tumours, which support the development of selumetinib in patients with MEK-dependent cancers.
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, which is present in 20 per cent of human cancers and 20-30 per cent of NSCLC tumours.
AstraZeneca is also investigating the potential for selumetinib in several types of MEK-dependent cancers. A phase II study assessing the efficacy and tolerability of selumetinib combined with radioactive iodine (RAI) as adjuvant therapy in patients with differentiated thyroid cancer with high risk of recurrence started in August 2013, and a further phase II study assessing the clinical efficacy and tolerability in combination with dacarbazine in patients with metastatic uveal melanoma is planned to start in late 2013.
Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule drugs to treat patients afflicted with cancer.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases.