SYDNEY, Dec. 10, 2020 /PRNewswire/ -- 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 PNOC
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
Adaptive Research
|
NCT03970447
|
DIPG &
DMGs
|
I
|
St Jude Children's
Research Hospital
|
NCT03696355
|
DIPG &
DMGs
|
N/A*
|
Pacific Pediatric
Neuro-Oncology Consortium
|
(TBD)
|
Breast Cancer Brain
Metastases
|
II
|
Dana-Farber Cancer
Institute
|
NCT03765983
|
Brain
Metastases
|
II
|
Alliance for Clinical
Trials in Oncology
|
NCT03994796
|
Brain
Metastases
|
I
|
Memorial
Sloan-Kettering Cancer Center
|
NCT04192981
|
Primary CNS
Lymphoma
|
II
|
Dana-Farber Cancer
Institute
|
(TBD)
|
*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.
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SOURCE Kazia Therapeutics Limited