Country for PR: China
Contributor: PR Newswire Asia (China)
Tuesday, September 22 2020 - 12:24
Kazia Enters Clinical Collaboration With Dana-farber Cancer Institute For Primary CNS Lymphoma
SYDNEY, Sept. 22, 2020 /PRNewswire-AsiaNet/ --

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 
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 

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 

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 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 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. 



 Kazia Therapeutics


 St Jude Children's Research Hospital
Breast Cancer Brain Metastases

(with trastuzumab)
 Dana-Farber Cancer Institute
Brain Metastases


 Alliance for Clinical Trials in Oncology
Brain Metastases

(with radiotherapy)

 Memorial Sloan-Kettering Cancer Center
Primary CNS Lymphoma

 Dana-Farber Cancer Institute

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