Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Developmental therapeutics

1335 - Phase I dose escalation study of M2698, a p70S6K/AKT inhibitor, in patients with advanced cancer


09 Sep 2017


Developmental therapeutics


Clinical Research


A Tsimberidou


Annals of Oncology (2017) 28 (suppl_5): v122-v141. 10.1093/annonc/mdx367


A.M. Tsimberidou1, C. Verschraegen2, A. Weise3, J. Sarantopoulos4, G. Lopes5, J. Nemunaitis6, A. Victor7, J. Shaw8, R. Kaleta8, R. Kurzrock9

Author affiliations

  • 1 Investigational Cancer Therapeutics, MD Anderson Cancer Center, TX77030 - Houston/US
  • 2 Division Of Medical Oncology, Ohio State Unv. Medical Center, Columbus/US
  • 3 Medical Oncology, Karmanos Cancer Institute, Detroit/US
  • 4 Institute For Drug Development, Cancer Therapy and Research Center at University of Texas Health Science Center, San Antonio/US
  • 5 Clinical Medicine, Sylvester Comprehensive Cancer Center, Miami/US
  • 6 Medical Oncology, Mary Crowley Cancer Research Center, Dallas/US
  • 7 Global Biostatistics, Merck KGaA, Darmstadt/DE
  • 8 Clinical Oncology, EMD Serono, Billerica/US
  • 9 Clinical Science, UCSD Moores Cancer Center, La Jolla/US


Abstract 1335


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


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


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 


M2698 was well tolerated and provided stable disease over a wide range of doses.

Clinical trial identification


Legal entity responsible for the study

Merck KGaA, Darmstadt, Germany


Merck KGaA, Darmstadt, Germany


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.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.