Interim Results of Phase 2 GBM Trial Released

Just released  - the drug has achieved results in GBM cancers (brain), which exceed that of many other multi billion dollar cancers drugs, already on the market.

What's more Paxalisib has achieved these results in this most difficult environment of the brain - as a monotherapy (single agent).

The Kazia trial treated patients with unmethylated O₆-methylguanine-methyltransferase (MGMT) promotor status, GBM brain cancer, where there is no other alternative drug treatment.  (chemotherapy drugs ineffective) The release comes from absolutely the world leading brain cancers experts....and will be the subject of a further presentation at SNO on the 19th next week.


CTNI-44. INTERIM RESULTS OF PHASE 2 STUDY TO EVALUATE PI3K/mTOR INHIBITOR PAXALISIB (GDC-0084) GIVEN TO NEWLY DIAGNOSED GLIOBLASTOMA PATIENTS WITH UNMETHYLATED O₆-METHYLGUANINE-METHYLTRANSFERASE PROMOTER

Patrick Wen, John de Groot, James Battiste, Samuel Goldlust, Denise Damek, James Garner, Jeremy Simpson, Alan Olivero, Timothy Cloughesy
Neuro-Oncology, Volume 22, Issue Supplement_2, November 2020, Page ii52, https://doi.org/10.1093/neuonc/noaa215.210
Published:

09 November 2020

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Abstract

BACKGROUND
Paxalisib (GDC-0084) is a potent, oral, selective small molecule inhibitor of class I phosphoinositide 3-kinase and mammalian target of rapamycin (PI3K/mTOR). Paxalisib crosses the blood-brain barrier and achieves a brain / plasma ratio of approximately 1.0. An MTD of 60mg per day has been identified in newly diagnosed glioblastoma (GBM) patient with unmethylated O₆-methylguanine-methyltransferase (MGMT) promotor status. Paxalisib has shown encouraging indications of clinical activity.


METHODS
This study has a 2-part design: an open-label, dose-escalation phase (Stage 1) to define MTD, followed by an expansion cohort (Stage 2) at the MTD and patients are randomized to take paxalisib, in fed or fasted states. Pharmacokinetic data will be analysed and compared by dose and fed/fasted status.

RESULTS
Stage 2 (expansion cohort) is fully enrolled and patients are in follow-up. Adverse event profile seems broadly consistent with prior clinical experience and with other PI3K-targeting agents. With analysis including all patients, a sustained PFS signal of 8.5 months is seen and this compares favourably with historical control .CONCLUSION
Paxalisib displays a safety profile consistent with previous data and promising efficacy signals in newly diagnosed GBM. A pivotal study in GBM is planned to commence recruitment later this year.