SYDNEY, Oct. 16, 2020
/PRNewswire/ -- Kazia Therapeutics Limited (ASX: KZA; NASDAQ:
KZIA), an Australian oncology-focused biotechnology company, is
pleased to announce that it has executed a definitive agreement
with the Global Coalition for Adaptive Research (GCAR) to commence
Kazia's participation in the GBM AGILE pivotal study in
glioblastoma. The study will open a new arm with Kazia's
investigational new drug, paxalisib (formerly GDC-0084), and will
now move into an operational phase with recruitment of patients to
the paxalisib arm expected to begin in Q1 CY2021.
Key Points
- GBM AGILE (NCT03970447) is intended to serve as the pivotal
study for registration of paxalisib in key markets
- Dr Ingo Mellinghoff (Memorial
Sloan Kettering Cancer Center) and Dr Eudocia Q Lee (Dana-Farber
Cancer Institute) have been named as Principal Investigators for
the paxalisib arm; Dr Timothy
Cloughesy (UCLA) is the
Principal Investigator for the overall study
- Kazia will pay an initial fee of US$ 5
million to GCAR, with further milestone payments payable
throughout the course of the study
- The duration of paxalisib's enrollment period in GBM AGILE is
expected to total approximately 30 – 36 months, plus follow-up, but
will depend on emerging study data, recruitment rates, and other
variables
Kazia CEO, Dr James Garner,
commented, "we have spent the last nine months or so working
closely with the GCAR team to plan paxalisib's entry into GBM
AGILE, and we are very gratified to now be moving into the
operational phase of the study. GBM AGILE is truly a
ground-breaking clinical trial, driven by some of the world's
leading experts in the field, and we are proud to be a part of it.
We expect GBM AGILE to provide definitive clinical evidence for the
approval of paxalisib by regulatory agencies in key markets. This
is a faster, more cost effective, and higher quality study than any
company of our size could mount independently, and we are confident
that it will provide the best possible opportunity for paxalisib to
demonstrate its potential in this very challenging disease."
Dr Meredith Buxton, Chief
Executive Officer at GCAR added, "We are pleased to welcome
paxalisib into GBM AGILE. Our mission is to help drive the
development of new therapies for glioblastoma, by creating an
efficient model for testing and confirming new potentially
beneficial treatments for patients with GBM. We look forward to
continuing to work closely with the Kazia team to bring paxalisib
into the study and support its evaluation."
Principal Investigators
Dr Ingo Mellinghoff and Dr
Eudocia Q Lee will serve as Principal Investigators for the
paxalisib arm. Dr Timothy Cloughesy
is the Principal Investigator for the overall study.
Dr Mellinghoff is the Chair of the Department of Neurology at
Memorial Sloan Kettering Cancer Center in New York, NY. He is a highly experienced
neuro-oncologist with an extensive track record of published
research in brain tumours, and is a Professor at the Gerstner Sloan
Kettering Graduate School of Biomedical Sciences and the Graduate
School of Medical Sciences at Weill Cornell
University. His laboratory focuses on the study of
biochemical pathways that regulate the growth of brain cancer, and
he has participated in numerous clinical trials for glioblastoma
and other forms of brain cancer.
Dr Mellinghoff commented, "we have seen little progress in the
treatment of glioblastoma for over two decades, and the need for
new therapies is urgent. We have seen encouraging signals from the
paxalisib program thus far, and my colleagues and I look forward to
exploring its potential in the GBM AGILE pivotal study."
Dr Lee is a neuro-oncologist at Dana-Farber Cancer Institute in
Boston, MA, Director of Clinical
Research at the Center for Neuro-Oncology at Dana-Farber, and an
Assistant Professor of neurology at Harvard
Medical School. She is a widely published clinical
researcher, with a primary research interest in tumours of the
brain and spinal cord, and their neurologic complications. Dr Lee
has been an investigator in previous clinical trials of paxalisib
in glioblastoma and has first-hand clinical experience with the
drug.
Dr Lee added, "GBM AGILE has been designed to provide a
definitive assessment of the efficacy of new drugs for
glioblastoma. Paxalisib has already been evaluated in two clinical
trials in this disease, and GBM AGILE will now greatly enrich our
understanding of how best to use it for the benefit of
patients."
GBM AGILE
GBM AGILE (Glioblastoma Adaptive Global Innovative Learning
Environment) is an international platform study that has been
established specifically to facilitate the approval of new
medicines for glioblastoma.
The scientific leadership of GBM AGILE comprises many of the
leading experts in glioblastoma, and they have worked in
collaboration with the US FDA on its development. It is sponsored
by the Global Coalition for Adaptive Research (GCAR), a US-based
501(c)(3) non-profit organisation. At present, the study is
underway in 30 sites in the United States and Canada, with plans to
launch in Europe and China during CY2021. One drug candidate is
currently participating, and paxalisib will be the second candidate
to join the study.
GBM AGILE is an adaptive study, so the number of patients
recruited, and their allocation within the study, will be
continuously adjusted in the light of emerging results. It is
expected that between 50 and 200 patients will receive paxalisib,
depending on the safety and efficacy of the drug. The data from
these patients will be compared against data from an estimated
several hundred patients in a shared control arm, allowing for
considerable operational efficiency.
The paxalisib arm of GBM AGILE will recruit newly diagnosed
patients with unmethylated MGMT promotor status, which is the same
population that has been investigated in Kazia's ongoing phase II
study. In addition, GBM AGILE will recruit recurrent patients to
the paxalisib arm. The drug may ultimately be considered
efficacious in either or both of these patient groups, and Kazia
will frame any future application for regulatory approval on the
basis of this data.
Dr Mellinghoff added, "we see interesting signals of activity in
the phase I study of paxalisib in recurrent glioma patients, and so
my colleagues and I consider it important to evaluate the drug also
in this later-stage group, where the unmet medical need is very
substantial. Including both newly diagnosed and recurrent patients
in GBM AGILE enables us to observe how paxalisib performs across
the spectrum of the disease, and provides us with a significant
amount of additional data as we move towards registration."
The primary endpoint of GBM AGILE is overall survival (OS),
which is considered the gold standard endpoint for the assessment
of new cancer therapies.
Indicative Costs and Timelines
Kazia will initially pay a fee of US$ 5
million to GCAR in consideration for paxalisib joining GBM
AGILE. Additional payments will be due throughout the duration of
the study, dependent on the attainment of key milestones. The full
financial terms of the agreement between Kazia and GCAR are
considered commercially confidential. In addition, the total cost
of the study will depend on the number of patients ultimately
recruited and other operational variables.
Kazia and GCAR expect that necessary regulatory filings and
submissions to institutional review boards will be actioned during
4Q CY2020. First patient in to the paxalisib arm is currently
anticipated to occur early in CY2021.
The duration of paxalisib's participation in GBM AGILE is
unpredictable due to the adaptive nature of the study. As an
indicative base case estimate, Kazia expects at this stage that
paxalisib will enrol patients for between 30 – 36 months, plus
follow-up. However, this figure could change, either in an upward
or downward direction, depending on emerging data from the study as
well as operational matters such as recruitment rates.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (ASX: KZA, NASDAQ: KZIA) is an
innovative oncology-focused biotechnology company, based in
Sydney, Australia. Our pipeline
includes two clinical-stage drug development candidates, and we are
working to develop therapies across a range of oncology
indications.
Our lead program is paxalisib (formerly GDC-0084), a small
molecule inhibitor of the PI3K / AKT / mTOR pathway, which is being
developed to treat glioblastoma, the most common and most
aggressive form of primary brain cancer in adults. Licensed from
Genentech in late 2016, paxalisib entered a phase II clinical trial
in 2018. Interim data was reported most recently at AACR in
June 2020, and further data is
expected in 2H 2020. Five additional studies are in start-up or
ongoing in other forms of brain cancer. Paxalisib was granted
Orphan Drug Designation for glioblastoma by the US FDA in
February 2018, and Fast Track
Designation for glioblastoma by the US FDA in August 2020. In addition, paxalisib was granted
Rare Pediatric Disease Designation and Orphan Designation by the US
FDA for DIPG in August 2020.
TRX-E-002-1 (Cantrixil), is a third-generation benzopyran
molecule with activity against cancer stem cells and is being
developed to treat ovarian cancer. TRX-E-002-1 has completed a
phase I clinical trial in Australia and the
United States with the final data expected in the second
half of calendar 2020. Interim data was presented most recently at
the AACR conference in June 2020.
Cantrixil was granted orphan designation for ovarian cancer by the
US FDA in April 2015.
For more information, please visit
www.kaziatherapeutics.com.
This document was authorized for release to the ASX by
James Garner, Chief Executive
Officer, Managing Director.
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SOURCE Kazia Therapeutics Ltd