AstraZeneca acknowledged today that its non-small-cell lung cancer (NSCLC) candidate selumetinib missed its primary endpoint in a Phase III trial assessing the drug with docetaxel.
The combination of selumetinib and docetaxel failed to show progression-free survival as a second-line treatment in patients with KRAS mutation-positive (KRASm) locally advanced or metastatic NSCLC compared with placebo, AstraZeneca said.
Selumetinib did not have a significant effect on overall survival, the company added.
“A randomized Phase II trial showed promising activity of selumetinib in combination with docetaxel in patients with KRAS mutation-positive lung cancer. It is disappointing for patients that these results have not been confirmed in Phase III,” Sean Bohen, AstraZeneca evp, global medicines development and CMO, said in a statement.
SELECT-1 was an international trial with 510 randomized patients in over 200 centers. Patients received either selumetinib (75 mg, orally, twice daily) or placebo in combination with docetaxel (intravenously, 75 mg/m2, on day one of every 21-day cycle).
Bohen added that AstraZeneca expects to present data from SELECT-1 at a forthcoming medical meeting, adding: “We remain committed to further developing treatments in the lung cancer setting, such as our immunotherapy combinations and targeted EGFR [epidermal growth factor receptor] treatments.”
SELECT-1 represents selumetinib’s second Phase III failure in as many years. In July 2015, AstraZeneca said the candidate did not meet its primary endpoint of progression-free survival in the Phase III SUMIT study assessing selumetinib with dacarbazine for the treatment of patients with metastatic uveal melanoma.
Selumetinib (also known as AZD6244 and ARRY-142886) is an inhibitor of MEK ½, a critical component of the RAS-ERK pathway, activation of which is implicated in driving cancer growth and progression, including in patients with KRASm NSCLC.
Selumetinib is also under study for adjuvant treatment of patients with stage III or IV differentiated thyroid cancer (DTC), for which the treatment received the FDA’s Orphan Drug Designation in May, and in patients with neurofibromatosis type 1.
AstraZeneca said it remained committed to developing selumetinib, including in Phase III trials in patients with DTC, and in a U.S. National Cancer Institute-sponsored Phase II registration trial in pediatric neurofibromatosis type 1 patients.
AstraZeneca acquired exclusive worldwide rights to selumetinib from Array BioPharma in 2003 in return for the pharma giant agreeing to pay Array $10 million upfront, research funding, potential development milestones of over $85 million, depending upon the number of successfully commercialized products, and royalties on product sales.