GSK1059615 is dosed orally once daily for 21 days of a 28-day cycle. Patients continue treatment for subsequent cycles as long as eligible and receiving benefit.

GSK1059615 is a potent PI3K-mTOR duel inhibitor, was tested PI3K-AKT-mTOR signaling in GSK1059615-treated cells. The treatment with GSK1059615 (3 μM) in SCC-9 cells and “OCC1” primary cancer cells dramatically inhibited phosphorylation of PI3K p85 (Tyr-458), AKT (Ser-473), mTOR (Ser-2448) and S6K1 (Thr-389). Thus, GSK1059615 apparently blocked PI3K-AKT-mTOR signaling cascade activation in head and neck squamous (HNSCC) cells. Remarkably, the basal activation of PI3K-AKT-mTOR cascade was quite low in the oral epithelial cells (“Oepi1”). p-PI3K p85, p-AKT, p-mTOR and p-S6K1 were almost undetected in the epithelial cells. These might explain why these epithelial cells were not killed by. Interestingly, ERK activation, tested by p-ERK1/2 (Thr-202/Tyr-204), was not altered by the same GSK1059615 (3 μM) treatment. Thus, GSK1059615 blocks PI3K-AKT-mTOR activation in HNSCC cells.