The Principal Investigator for the study, Professor Sabine Mueller, commented, “No individual drug
therapy has ever shown convincing efficacy in this group of patients. We plan to apply novel trial design methodologies to understand the potential for combination therapy, using some of the most promising agents in the global pipeline, to change
the outcome in this devastating disease.”
Kazia CEO, Dr James Garner, commented, “We are proud to be part of this important and innovative
clinical study. Preclinical data supports the potential for paxalisib to combine well with certain other therapies, and we are keen to see if this approach is similarly promising in the clinic. There remains a desperate need for new treatment
options in this disease, and we hope that paxalisib may be able to contribute to better outcomes for patients and their families.”
Clinical Trial
Design
PNOC022 will enrol children and young adults with diffuse midline gliomas, a category of brain tumours that includes DIPG. The study will
include separate cohorts comprising patients with newly diagnosed disease, patients who have completed initial radiotherapy, and patients who have experienced disease progression after treatment.
At the outset, all patients will be treated with ONC201, combined with either paxalisib or panobinostat. The study employs an adaptive design, in which
different arms will be opened and closed based on emerging preclinical and clinical data. The primary endpoint will be the proportion of patients who are progression-free at six months (PFS6) for newly diagnosed patients, and overall survival (OS)
for recurrent patients.
The lead investigator, Professor Sabine Mueller, is a board-certified neurologist and paediatric neuro-oncologist whose research
focuses on novel therapies in childhood brain cancer. Professor Mueller holds an academic appointment in the Department of Neurology, Neurosurgery and Pediatrics at the University of California, San Francisco (UCSF) and serves as head of the
clinical program at the DMG Centre at the Children’s Hospital of the University of Zurich. She obtained her medical degree from the University of Hamburg and also holds a PhD in molecular biology.
The design of the PNOC022 study has been extensively informed by laboratory research in DIPG, and in particular, by research undertaken at the University of
Newcastle, Hunter Medical Research Institute (HMRI) in Australia by Associate Professor Matt Dun and colleagues. The HMRI team has conducted laboratory research with paxalisib for several years and has generated a powerful body of data combining
paxalisib with other investigational drugs. This research has been partly funded by RUN DIPG, a not-for-profit organisation led by Associate Professor Dun, the DIPG
Collaborative, Chad Tough Defeat DIPG Foundation, and the McDonald Jones Foundation.