SYDNEY, Sept. 22, 2020 /PRNewswire/ -- Kazia
Therapeutics Limited (ASX: KZA; NASDAQ: KZIA), an Australian
oncology-focused biotechnology company, is pleased to announce that
it has entered into a collaboration with Dana-Farber Cancer
Institute (DFCI) in the United
States, to investigate the use of Kazia's investigational
new drug, paxalisib (formerly GDC-0084), in primary central nervous
system (CNS) lymphoma, a potential new indication for the drug.
Key Points
- Lymphoma is a cancer of white blood cells. It occurs in the
lymphatic system and can spread almost anywhere in the body;
primary CNS lymphoma (PCNSL) occurs exclusively in the brain and
central nervous system
- The PI3K inhibitor class is well validated in lymphoma outside
the brain; three of the four FDA-approved PI3K inhibitors are
treatments for forms of lymphoma, but they are assumed ineffective
for PCNSL since they cannot cross the blood-brain barrier
- DFCI will initiate an open-label phase II clinical trial of
paxalisib in PCNSL
- The study is expected to recruit up to 25 patients, taking up
to 2 years to complete
- Kazia will provide support including study drug and a financial
grant
- This study will be the sixth ongoing clinical trial of
paxalisib in brain cancer
Dana-Farber Cancer Institute (DFCI) is a world-leading cancer
treatment and research centre, based in Boston, Massachusetts. It is a principal
teaching affiliate of Harvard Medical
School and has been designated a Comprehensive Cancer Center
by the US National Cancer Institute. DFCI participates in as many
as 600 clinical trials at any given time and has been an important
contributor to the development of many important new cancer
therapies.
Kazia CEO, Dr James Garner,
commented, "this is an exciting new opportunity for the paxalisib
program. We are delighted to support the team at Dana-Farber to
explore the potential for paxalisib to benefit patients with PCNSL.
Dana-Farber is one of the world's leading centres of excellence in
this disease, so we are immensely fortunate to be working with
them. We are pleased also to see a new and important target added
to the broader paxalisib clinical program, and we look forward to
seeing the project commence."
Kazia's financial support to the study will use a portion of the
funds contributed by shareholders in the Share Purchase Plan (SPP)
conducted in May 2020.
Primary CNS Lymphoma
Lymphoma is a haematological malignancy (blood cancer) that
originates from lymphocytes, a type of white blood cell involved in
the immune system. PCNSL is a specific form of the disease that
originates in the brain and central nervous system.
Three of the four PI3K inhibitors approved by the US Food and
Drug Administration (FDA) are treatments for various forms of
lymphoma, provide a strong validation for PI3K as a target in this
disease. Paxalisib is the only PI3K inhibitor in mainstream
development with the ability to penetrate the blood-brain barrier,
and as such has a unique rationale for development in PCNSL.
PCNSL accounts for approximately 4% of brain tumours, and the
incidence is increasing with time. Patients are typically in their
60s or older, and the disease is slightly more common in
men.[1] The mainstays of treatment comprise chemotherapy
and radiotherapy, but recurrence is common and only approximately
30% of patients remain alive five years after
diagnosis.[2] Many of the drugs used to treat lymphoma
elsewhere in the body are ineffective in PCNSL due to their
inability to cross the blood-brain barrier.
Clinical Trial Design
Dana Farber Cancer Institute will launch a single-arm phase II
clinical trial in patients with relapsed or refractory PCNSL, who
are resistant to existing treatments. The primary endpoint will be
to assess efficacy via overall response rate (ORR), which measures
the ability of paxalisib to shrink tumours. Safety and other
efficacy endpoints will also be captured. The study will also
examine tissue and cerebrospinal fluid samples to identify
potential predictors of response.
The principal investigator for the study is Dr Lakshmi Nayak,
Director of the CNS Lymphoma Center at Dana-Farber Cancer
Institute. Dr Nayak is an Assistant Professor of Neurology at
Harvard Medical School and a
board-certified neuro-oncologist. Her research interests focus on
metastatic brain cancer, glioblastoma, and PCNSL, and she is
extensively published in the field of brain cancer. She has been an
investigator for multiple clinical trials of experimental drugs in
this disease area.
Commencement of recruitment to the study is expected in early
CY2021, but is subject to receiving necessary approvals from FDA
and from institutional review boards. The study will be listed on
clinicaltrials.gov closer to the commencement of recruitment.
Dana-Farber Cancer Institute
The CNS Lymphoma Center (CNSLC) at Dana-Farber / Brigham and
Women's Cancer Center is the first centre of its kind in the world
dedicated to providing comprehensive care and research for patients
with primary or secondary CNS lymphoma. With the most advanced
treatment options available — including surgery, chemotherapy, stem
cell transplant, radiation therapy, immunotherapy, and targeted
therapies, and with extensive clinical trial options - CNSLC is
uniquely qualified to treat patients with CNS lymphoma and advance
the outcome of patients with these tumors.
Other clinicians at Dana-Farber Cancer Institute are currently
involved in clinical trials of paxalisib in other forms of brain
cancer. Dr Jose Pablo Leone is the
principal investigator on a phase II clinical trial of paxalisib in
combination with Herceptin (trastuzumab) for breast cancer brain
metastases (breast cancer that has spread to the brain). Professor
Patrick Wen has been centrally
involved in the ongoing phase II study of paxalisib in
glioblastoma, and plays a leadership role in the international GBM
AGILE study.
Paxalisib Clinical Program
The initiation of this trial in PCNSL brings the number of
ongoing clinical studies of paxalisib in brain cancer to six.
Indication
|
Phase
|
Sponsor
|
Registration
|
Glioblastoma
|
II
|
Kazia
Therapeutics
|
NCT03522298
|
DIPG
|
I
|
St Jude Children's
Research Hospital
|
NCT03696355
|
Breast Cancer Brain
Metastases
(with
trastuzumab)
|
II
|
Dana-Farber Cancer
Institute
|
NCT03765983
|
Brain
Metastases
|
II
|
Alliance for Clinical
Trials in Oncology
|
NCT03994796
|
Brain
Metastases
(with
radiotherapy)
|
I
|
Memorial
Sloan-Kettering Cancer Center
|
NCT04192981
|
Primary CNS
Lymphoma
|
II
|
Dana-Farber Cancer
Institute
|
(TBD)
|
Next Steps
Recruitment to this study is expected to commence in 1H
CY2021.
Kazia completed recruitment to a phase II clinical trial of
paxalisib in newly-diagnosed glioblastoma in February 2020, and interim clinical data was
presented at the AACR Virtual Annual Meeting II in June 2020. Overall survival was calculated at
17.7 months, which compares favourably to an historical figure of
12.7 for temozolomide, the existing FDA-approved standard of care.
Kazia expects to present further data from this study in 2H CY2020,
and to conclude the study in early CY2021.
[1] J
Rubenstein et al. (2008) Leuk Lymphoma 49(0
1):43-51
|
[2] MS Shiels et al. (2016) Br J
Haematol. 174(3):417-424
|
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SOURCE Kazia Therapeutics Limited