0000000000650675
AUTHOR
Joaquin Mateo
Beyond the lessons learned from the COVID-19 pandemic: opportunities to optimize clinical trial implementation in oncology.
Abstract The COVID-19 pandemic affected millions of people globally with lasting effects on society, patients, investigators and health institutions. Clinical trials, our best tool to improve cancer treatment for patients through testing the clinical value of a new treatment, have been affected by the pandemic. The pandemic footprint represents both a risk of compromising development of new therapies and an opportunity to elicit discussion over a portfolio of broader reforms, applicable irrespective of pandemics, in order to improve the design and implementation of clinical trials in oncology. The administrative load should be reduced, without affecting the quality of research and principle…
PI3K/AKT Activation and Response in Phase IB: AKT Inhibitor GDC-0068 with Docetaxel (D) Or MFOLFOX6 (F) in Refractory Solid Tumors
R. Meng1, L. R. Molife2, L. de Mattos-Arruda3, A. Hollebecque4, S. J. Isakoff5, D. Roda6, Y. Yan1, A. Cervantes6, J. C. Soria4, J. Mateo2, G. Argiles3, J. C. Bendell7 Genentech, South San Francisco, CA, USA, Institute of Cancer Research/ Royal Marsden Hospital, Sutton, United Kingdom, Vall d’Hebron University Hospital, Barcelona, Spain, Institut Gustave Roussy, Villejuif, France, Massachusetts General Hospital, Boston, MA, USA, Institute of Health Research INCLIVA, University of Valenica, Valencia, Spain, Sarah Cannon Research Institute, Nashville, TN, USA
A phase Ib study of the Akt inhibitor GDC-0068 with docetaxel (D) or mFOLFOX-6 (F) in patients (pts) with advanced solid tumors.
3021 Background: Activation of the Akt pathway is observed in multiple tumors and may contribute to chemoresistance. GDC-0068 is an ATP-competitive small molecule inhibitor of all three isoforms of Akt; in a phase Ia study, it was well tolerated with maximum tolerated dose (MTD) of 600 mg daily (21 days on/7days off) and pharmacodynamic down-regulation of Akt signaling in tumors at doses ≥100 mg. In vitro, GDC-0068 shows synergism with cytotoxic agents. This phase Ib study defines the dose limiting toxicities (DLT), MTD, safety and pharmacokinetics (PK) of GDC0068 in combination with D and F. Methods: Using a 3+3 designeligible patients (pt) with advanced/metastatic solid tumors were treat…