Country for PR: China
Contributor: PR Newswire Asia (China)
Thursday, December 10 2020 - 16:22
Kazia to Collaborate with Pacific Pediatric Neuro-Oncology Consortium (PNOC) for New Paxalisib Combination Study in DIPG
SYDNEY, Dec. 10, 2020 /PRNewswire-AsiaNet/ --

Kazia Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian 
oncology-focused biotechnology company, is pleased to announce that it has 
executed a Letter of Intent with the Pacific Pediatric Neuro-Oncology 
Consortium (PNOC) to launch a clinical trial of multiple therapies, including 
Kazia's investigational new drug, paxalisib (formerly GDC-0084), in diffuse 
midline gliomas including diffuse intrinsic pontine glioma (DIPG). 

The new clinical trial, PNOC022, will employ an adaptive trial design to test 
several therapies in different combinations and in different subsets of 
patients. In addition to paxalisib, the other therapies involved will initially 
include ONC201, manufactured by Oncoceutics, Inc, and panobinostat, 
manufactured by SecuraBio, Inc. The study is expected to open initially in the 
United States and will then expand to other countries during CY2021. 

Key Points
-PNOC022 uses cutting-edge clinical trial design to efficiently and rapidly 
evaluate combination therapies in DIPG, under the leadership of world experts 
in the field 
-Lead investigator is Professor Sabine Mueller, a leading paediatric 
neuro-oncologist and co-founder of PNOC 
-Study is guided by Australian research at University of Newcastle, under 
leadership of Associate Professor Matt Dun, who serves as a scientific advisor 
-Combination approach builds on recent positive data from St Jude SJPI3K study 
(NCT03696355) with paxalisib as single agent in DIPG, and brings together 
several of the most promising candidates in the global pipeline for DIPG 
-Kazia will provide paxalisib investigational product; study is fully funded by 

Kazia CEO, Dr James Garner, commented, "DIPG and diffuse midline gliomas have 
emerged as an exciting second front in the development of paxalisib as a brain 
cancer therapy. Work by Dr Chris Tinkle and colleagues at St Jude Children's 
Research Hospital has taught us a great deal about how to use this drug in a 
paediatric population. In parallel, extensive laboratory research by Associate 
Professor Matt Dun and colleagues has generated a rich and comprehensive data 
set to inform combination use. We are delighted to now have the opportunity to 
work with the PNOC team to bring these insights together and to take paxalisib 
into the next chapter of its development as a potential therapy for DIPG." 

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 opened and closed based on emerging preclinical and 
clinical data. The primary endpoint will be the proportion of patients 
progression-free at six months (PFS6) for newly diagnosed patients, and overall 
survival (OS) for recurrent patients.

The lead investigator will be Professor Sabine Mueller, 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 programme 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.

Professor Mueller commented, "DIPG remains one of the most challenging of 
childhood cancers. No drug treatment has ever demonstrated meaningful efficacy. 
The PNOC022 study brings a different approach, uniting the best of preclinical 
research with novel clinical trial techniques. We look forward to commencing 
enrolment to the study shortly, and very much hope that we are able to generate 
new hope for patients and their families."

Commencement of the study remains subject to execution of a definitive contract 
and is dependent on approval by the US FDA and Institutional Review Boards. It 
is expected that PNOC022 will initially open in the United States in 1H CY2021, 
with expansion to other countries taking place in CY2021. Discussions are 
ongoing regarding the potential inclusion of Australian sites in the study.

Australian Scientific Research

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) 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, Defeat DIPG Michael Moiser Foundation and the 
McDonald Jones Foundation. The robust mechanistic data is expected to be 
published in high impact scientific journals in coming months. 

Pacific Pediatric Neuro-Oncology Consortium (PNOC)

The Pacific Pediatric Neuro-Oncology Consortium (PNOC) is an international 
consortium, with study sites in the United States, Canada, Swizterland, Europe, 
India, Israel, and Australia. PNOC is dedicated to bringing new therapies to 
children and young adults with brain tumours, using the latest scientific 
understanding to inform a personalised medicine approach.

PNOC comprises 225 leading specialists in childhood brain cancer and is 
currently driving sixteen international clinical trials. In Australia, the 
organisation collaborates closely with the Australia and New Zealand Children's 
Hematology / Oncology Group (ANZCHOG). PNOC's research is substantially 
supported by the PNOC Foundation, the Pediatric Brain Tumor Foundation, and 
other not-for-profit entities.

Paxalisib Clinical Program

The initiation of this trial will bring the number of ongoing clinical studies 
of paxalisib in brain cancer to eight.

Indication       Phase      Sponsor                 Registration
Glioblastoma      II         Kazia Therapeutics        NCT03522298
Glioblastoma      II / III   Global Coalition for      NCT03970447
                              Adaptive Research
DIPG & DMGs       I          St Jude Children's        NCT03696355
                              Research Hospital
DIPG & DMGs       N/A*       Pacific Pediatric         (TBD)
Breast Cancer     II         Dana-Farber Cancer        NCT03765983
Brain Metastases              Institute
Brain Metastases  II         Alliance for Clinical     NCT03994796
                              Trials in Oncology
Brain Metastases  I          Memorial Sloan-Kettering  NCT04192981
                              Cancer Center
Primary CNS       II         Dana-Farber Cancer        (TBD)
Lymphoma                      Institute

*Note - the PNOC022 has not adopted a 'phase' designation and is described as 
an 'adaptive platform study'

Next Steps

Recruitment to this study is expected to commence in 1H CY2021.

SOURCE: Kazia Therapeutics Limited