Abstract 1335
Background
Aberrant PI3K/Akt/mTOR (PAM) pathway signaling is observed in various tumors and confers resistance to standard therapies. M2698 is an oral, brain penetrant, potent and selective p70S6K/Akt1/3 inhibitor that can block signaling from Akt feedback loop activation, a possible tumor escape mechanism
Methods
Patients (pts) with advanced cancer were given oral M2698 daily (PO 15–380 mg) in 21-day (d) cycles in a 3 + 3 dose escalation [DE] design. Response was assessed every 2 cycles. An expansion phase in pts with PAM pathway tumor alterations is ongoing
Results
Overall, 50 pts received M2698 monotherapy (DE, n = 40; expansion, n = 10); DE data presented only (cut-off 10/27/16). Treated pts had a median age of 56 years. (14 men, 26 women). Tumor types included breast (n = 7), colon (n = 4), lung (n = 4) and other (n = 25). In the DE phase, 35/40 pts were evaluable. Two pts had a dose limiting toxicity (DLT; 60mg and 160mg) and drug-related Grade ≥3 adverse events (AEs) occurred in 6/40 (15%) of pts. AEs leading to dose reductions occurred in 1 pt at
Conclusions
M2698 was well tolerated and provided stable disease over a wide range of doses.
Clinical trial identification
NCT01971515
Legal entity responsible for the study
Merck KGaA, Darmstadt, Germany
Funding
Merck KGaA, Darmstadt, Germany
Disclosure
G. Lopes, R. Kurzrock: Research funding from Merck. A. Victor: Merck employee. J. Shaw, R. Kaleta: EMD Serono employee. All other authors have declared no conflicts of interest.