AstraZeneca has announced the first patient randomized in a phase III clinical trial 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 tumors are KRAS mutation-positive.
In 2003, Array BioPharma invented and licensed the worldwide rights to develop and commercialize selumetinib to AstraZeneca. 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.
“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,” noted Ron Squarer, Chief Executive Officer of Array BioPharma.
The 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 as the primary endpoint and Overall Survival 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 III in NSCLC followed the results from a randomized phase II 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).
“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 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,” said Antoine Yver, Vice President and Head of Oncology in AstraZeneca’s Global Medicines Development unit.
AstraZeneca is also investigating the potential for selumetinib in several types of MEK-dependent cancers. A pivotal 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.