AstraZeneca today announced the first patient randomized in a Phase 3 clinical trial for selumetinib, an oral, potent, selective MEK inhibitor, being investigatedas second-line therapy in patients with advanced or metastatic non-small-cell lung cancer (NSCLC) whose tumors are KRAS mutation-positive.
Array BioPharma invented and licensed worldwide rights to develop and commercialize selumetinib to AstraZeneca in 2003. The initiation of the Phase 3 trial triggered a $5 million milestone payment to Array. Array retains significant economic rights to selumetinib under the agreement with AstraZeneca, including double digit royalties on global commercial sales and the potential for approximately $70 million in additional milestone payments.
Ron Squarer, Chief Executive Officer, Array BioPharma noted, "The initiation of the Phase 3 SELECT-1 trial highlights AstraZeneca's on-going commitment to develop selumetinib broadly in areas of high unmet need. Together with the active pivotal trial in thyroid cancer and the announced uveal melanoma trial, there are already three paths to market for selumetinib." The SELumetinib Evaluation as Combination Therapy-1 (SELECT-1) study is a randomized, 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) as the primary endpoint and Overall Survival (OS) as a secondary endpoint. AstraZeneca has reported that SELECT-1 will include 220 centers 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). 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.
AstraZeneca's decision to progress selumetinib to Phase 3 in NSCLC followed the results from a randomized Phase 2 study evaluating the combination of selumetinib with docetaxel against docetaxel alone in KRAS-mutation positive NSCLC. This study demonstrated a high and durable response rate of 37.2% vs 0% (p<0.0001), translating into a statistically significant improvement in PFS of 5.3 vs 2.1 months (HR 0.58, p<0.014).
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 3 study to investigate whether a MEK inhibitor in combination with chemotherapy is superior to chemotherapy alone in 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 2 results, which showed promising clinical activity in this group of patients." AstraZeneca is also investigating the potential for selumetinib in several types of MEK-dependent cancers. A pivotal Phase 2 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 2 study assessing the clinical efficacy and tolerability in combination with dacarbazine in patients with metastatic uveal melanoma is planned to start in late 2013.
About selumetinib 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 1 and Phase 2 clinical studies across a range of solid tumors, 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 tumors, including those featuring the KRAS mutation, which is present in 20% of human cancers and 20-30% of NSCLC tumors.