Date: 2016-08-09
Type of information: Results
phase: 3
Announcement: results
Company: AstraZeneca (UK)
Product: selumetinib and docetaxel
Action
mechanism: tyrosine kinase inhibitor/MEK inhibitor. 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% of human cancers and 20-30% of NSCLC tumours. AstraZeneca acquired exclusive worldwide rights to selumetinib from Array. To date, Array received $26.5 million in up-front and milestone payments and is entitled to potential additional development milestone payments of approximately $70 million (with $30 million specific for selumetinib) and royalties on product sales.
Disease: KRAS mutation-positive and metastatic non small cell lung cancer
Therapeutic area: Cancer - Oncology
Country: Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, France, Germany, Hungary, Israel, Italy, Mexico, The Netherlands, Peru, Poland, Portugal, Romania, Russian Federation, Spain, Sweden,Turkey, Ukraine, UK, USA
Trial
details: 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). 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). (NCT01933932)
Latest
news: * On August 9, 2016, AstraZeneca announced results from the Phase III SELECT-1 trial of the MEK 1/2 inhibitor, selumetinib, in combination with docetaxel chemotherapy as 2nd-line treatment in patients with KRAS mutation-positive (KRASm) locally-advanced or metastatic non-small cell lung cancer (NSCLC). The results showed that the trial did not meet its primary endpoint of progression-free survival (PFS), and selumetinib did not have a significant effect on overall survival (OS). The adverse event profiles for selumetinib and docetaxel were consistent with those seen previously.
In May 2016, selumetinib was granted Orphan Drug Designation by the FDA for adjuvant treatment of patients with stage III or IV differentiated thyroid cancer (DTC), and AstraZeneca is committed to exploring its full potential, including in Phase III trials in patients with DTC and in a US National Cancer Institute-sponsored Phase II registration trial in patients with paediatric neurofibromatosis type 1.* On October 22, 2013, AstraZeneca has announced the first patient randomised 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 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. 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.
* On May 16, 2013, AstraZeneca has announced that a Phase III study of selumetinib in combination with docetaxel as a second-line therapy for patients with KRAS mutation-positive and metastatic non small cell lung cancer is planned to commence in the second half of 2013.
