GDC-0980 (formerly RG7422) is in development by Genentech, a subdivision of Roche Pharmaceuticals (http://www.gene.com). GDC-0980 is designed to be a selective, dual inhibitor of PI3 Kinase and mTOR Kinase. PI3 Kinase is an oncogene that is commonly mutated in cancer. The PI3K/Akt/mTOR pathway regulates cell growth and survival and is felt to play a crucial role downsream of KIT signaling.
Click here to read a description of GDC-0980 by the manufacturer.
NCI Drug Dictionary definition: dual PI3 kinase/mTOR inhibitor GDC-0980 is an orally available agent targeting phosphatidylinositol 3 kinase (PI3K) and mammalian target of rapamycin (mTOR) kinase in the PI3K/mTOR signaling pathway, with potential antineoplastic activity. PI3K/mTOR kinase inhibitor GDC-0980 inhibits both PI3K kinase and mTOR kinase, which may result intumor cell apoptosis and growth inhibition of cancer cells overexpressing PI3K/mTOR. Activation of the PI3K/mTOR pathway promotes cell growth, survival, and resistance to chemotherapy and radiotherapy; mTOR, a serine/threonine kinase downstream of PI3K, may also be activated in a PI3K-independent fashion.
A Phase I dose escalation trial evaluating the safety, tolerability, and pharmokinetics of escalating doses of GDC-0980 administered on a daily vs. a weekly dosing schedule is being conducted on patients with incurable, locally advanced or metastatic solid malignancies or non-Hodgkin’s lymphoma. This drug is in the early stage of development and there are no trials specifically for GIST at present.
A preliminary report of the Phase I tials was given at the 2010 ASCO meeting. Link for the abstract.
A first-in-human, phase l study to evaluate the dual PI3K/mTOR inhibitor GDC-0980 administered QD in patients with advanced solid tumors or non-Hodgkin's lymphoma.
S. Dolly et al, ASCO 2010 Abstract 3079
An earlier paper was given at the 2009 AACR meeting. Link for the abstract.
Pharmacokinetics and pharmacodynamic biomarkers for the dual PI3K/mTOR inhibitor GDC-0980: Initial phase I evaluation
A.J. Wagner et al, Abstract B137
Click below to view the current trials available for GDC-0980 on the Clinicaltrials.gov website: