GIST Support Wiki

BYL719 plus Gleevec trial


The trial protocol for BYL719 plus Gleevec has been recently updated at to reflect which of the trial sites are open.

The trial is open in the USA at Dartmouth, University of Miami, and OHSU. I noted that the principle investigator listed for this trial at OHSU is a new name for us, Michael Mauro, who has been a long term CML hematologist at OHSU. Other open trial sites include several countries in Europe, but nothing in Asia.

Why is BYL719 important? This drug blocks a very important intracellular signaling protein called PI3K. Dyfunction of PI3K has been implicated in many types of cancers, and so there is much interest in PI3K inhibitors across the board.

PI3K tranduces activation signals coming from abnormal KIT into the cell. Blocking PI3K in GIST may be beneficial for a few reasons. Some resistant GIST may have acquired activating abnormalities for PI3K. When KIT can not be inhibited to a sufficient degree (secondary mutations in KIT or exon 9 KIT), blocking PI3K might "clog up the works" of KIT signals. And for wild type GIST, KIT is not the key target, but blocking an important signaling hub PI3K may synergize to some degree with KIT inhIBITION.