Promising data from a double-blind, randomized Phase 2 study conducted by AstraZeneca comparing the efficacy of selumetinib (AZD6244/ARRY-886) in combination with docetaxel versus docetaxel alone in 87 second-line patients with KRAS mutation positive locally advanced or metastatic non-small cell lung cancer (NSCLC) (Stage IIIB – IV) were presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. Array BioPharma Inc. (Nasdaq: ARRY) invented selumetinib and licensed worldwide rights to develop selumetinib to AstraZeneca under a collaboration agreement in 2003.
This study showed statistically significant improvement in progression-free survival, objective response rate, and alive and progression-free at six months as well as a trend for improvement in overall survival in favor of selumetinib in combination with docetaxel versus docetaxel alone.
The tolerability profile of selumetinib in combination with docetaxel was consistent with previously conducted studies. There was an increased incidence of Grade 3 or 4 neutropenia and febrile neutropenia and of Grade 1 or 2 diarrhea in patients receiving the selumetinib combination versus docetaxel alone.
Overall survival was longer for selumetinib in combination with docetaxel compared to docetaxel alone (9.4 mo vs 5.2 mo; 56 events, median follow-up 219 days) but did not reach statistical significance. Hazards were non-proportional (HR 0.80; 80% CI 0.56, 1.14; 1-sided p=0.2069). All secondary endpoints, including response rate (selumetinib/docetaxel 37%, docetaxel 0%; p<0.0001) and progression free survival (selumetinib/docetaxel 5.3 mo, docetaxel 2.1 mo; 71 events; HR = 0.58; 80% CI 0.42, 0.79; 1-sided p=0.0138), were significantly improved for selumetinib in combination with docetaxel versus docetaxel alone.“In the U.S., KRAS is the most prevalent oncogenic alteration in NSCLC with approximately 20 percent of patients harboring a KRAS mutation,” said Pasi A. Jänne, M.D., Ph.D., Primary Investigator and Associate Professor of Medicine, Harvard Medical School. “There are no targeted treatment options currently available for this subtype of NSCLC, so we are extremely delighted at this stage of development to see such promising results.”