Kazia Therapeutics Ltd welcomes start of PNOC study in childhood brain cancer, first patient enrolled

“There remains an urgent need for new treatment options for this disease, and we hope that paxalisib can contribute to better outcomes for patients and their families,” said Kazia CEO.

The investigational drug paxalisib from Kazia Therapeutics Ltd (ASX:KZA, NASDAQ:KZIA) has a role in PNOC022, a multidrug Phase II trial in DIPG and diffuse midline gliomas initiated at the University of California, San Francisco, in which the first patient was enrolled in the study.

Diffuse intrinsic pontine glioma (DIPG) is the most common of a group of childhood brain cancers known as diffuse midline gliomas (DMGs). The disease has no FDA-approved drug treatments, and the median survival after diagnosis is about 10 months.

Study includes paxalisib

PNOC022 includes paxalisib in the experimental arms and is expected to provide valuable data on the drug’s potential use in this highly aggressive form of childhood brain cancer.

The PNOC022 study (NCT05009992) is sponsored by the Pacific Pediatric Neuro-Oncology Consortium (PNOC), an international consortium focused on developing novel therapies for brain cancer.

It is an adaptive platform study that will examine multiple therapies simultaneously, both as single agents and in combination, to determine the optimal approach to treatment.

The lead investigator in the study is Professor Sabine Mueller, a board-certified neurologist and pediatric neuro-oncologist with a research program focused on novel therapies for brain tumors in children.

Applying new methodologies

Professor Mueller noted, “No single drug regimen has ever demonstrated convincing efficacy in this group of patients.

“We plan to apply novel research design methodologies to understand the potential for combination therapy, using some of the most promising agents in the global pipeline, to change the outcome of this devastating disease.”

PNOC022 will enroll children and young adults with diffuse midline gliomas, a class of brain tumors that also includes DIPG.

The study will include separate cohorts consisting of patients with newly diagnosed disease, patients who have completed initial radiotherapy, and patients who have experienced disease progression after treatment.

Initially, all patients will be treated with ONC201, combined with paxalisib or panobinostat. The study uses an adaptive design, opening and closing different arms based on emerging preclinical and clinical data.

The primary endpoint is the percentage of patients who are progression-free at six months (PFS6) for newly diagnosed patients and overall survival (OS) for recurrent patients.

“Need for new treatment options”

Kazia CEO Dr. James Garner said: “We are proud to be part of this important and innovative clinical trial. Preclinical data support the potential for paxalisib to combine well with certain other therapies, and we would like to see if this approach holds promise in the clinic as well.

“There remains an urgent need for new treatment options for this disease, and we hope that paxalisib can contribute to better outcomes for patients and their families.”

Kazia’s support for the project will primarily consist of providing investigational drug.

study design

The design of the PNOC022 study has been informed extensively by laboratory research in DIPG, and in particular by research 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 studies with paxalisib for several years and has generated a powerful body of data combining paxalisib with other investigational drugs.

This research was funded in part by RUN DIPG, a nonprofit led by Associate Professor Dun, the DIPG Collaborative, Chad Tough Defeat DIPG Foundation, and the McDonald Jones Foundation.

Associate professor Dun serves as scientific advisor to the study.

The study has the potential to recruit up to several hundred patients, with the actual number depending on emerging results.

About paxalisib

Kazia’s lead program is paxalisib, a brain-penetrating inhibitor of the PI3K/Akt/mTOR pathway, which is being developed for the treatment of glioblastoma, the most common and most aggressive form of primary brain cancer in adults.

Paxalisib received orphan drug designation for glioblastoma from the US FDA in February 2018 and Fast Track glioblastoma designation for glioblastoma in August 2020. August 2020.

The start of the PNOC022 study adds to the pipeline of nine ongoing clinical trials of paxalisib in various brain cancers.