SYDNEY, Aug. 5, 2022 /PRNewswire/ -- Kazia
Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused
drug development company, is pleased to announce the presentation
of promising new data from an ongoing phase I clinical trial of
paxalisib in combination with radiotherapy for the treatment of
brain metastases, sponsored by Memorial Sloan Kettering Cancer
Center in New York, NY.
Interim data from the first stage of the study reports that all
9 evaluable patients experienced complete or partial response,
representing an overall response rate (ORR) of 100%. For
comparison, a typical ORR associated with whole brain radiotherapy
alone can commonly range from 20-45% in published studies, of which
some representative examples are indicated below.
The data has been accepted for an oral presentation at the
upcoming 2022 Annual Conference on CNS Clinical Trials and Brain
Metastases, jointly organised by the Society for Neuro-Oncology
(SNO) and the American Society for Clinical Oncology (ASCO), and
held in Toronto, Canada from
12-13 August 2022.
Key Points
- Approximately 200,000 cancer patients develop brain metastases
in the United States each year.
Brain metastases are typically very challenging to treat and are
associated with poor prognosis. Radiotherapy remains a mainstay of
clinical management.
- Dr. Jonathan Yang, Director,
Metastatic Disease, Department of Radiation Oncology at Memorial
Sloan Kettering Cancer Center is the Principal Investigator of this
clinical trial that is examining the combination of paxalisib with
whole brain radiotherapy for patients with brain metastases
(NCT04192981). The trial is designed in two stages: an initial
exploratory stage and a confirmatory expansion stage.
- 9 of 12 patients in the initial stage were evaluable for
efficacy. All 9 patients exhibited complete or partial response,
according to RANO-BM criteria, representing an ORR of 100%.
- The patients comprised a range of primary tumours, with breast
cancer the most common, representing one third of patients.
- The safety profile of paxalisib in combination was broadly
consistent with monotherapy experience in other clinical trials,
and a maximum tolerated dose (MTD) of 45mg daily in combination
with radiotherapy was confirmed.
- Recruitment to the expansion stage has already commenced, with
the objective of recruiting an additional 12 patients.
Kazia CEO, Dr. James Garner,
commented, "We are encouraged by this data and by the potential
benefit it may indicate to this substantial and high-need group of
patients. Radiotherapy is a ubiquitous component of the treatment
paradigm for brain metastases, but resistance is common. Dr. Yang's
study has shown a very promising signal that paxalisib may help to
potentiate the effect of radiotherapy. We also learned recently
that the ongoing Alliance study in brain metastases had graduated
to an expansion stage in the breast cancer cohort, so this now
represents the second positive signal for paxalisib in brain
metastases, which we increasingly believe represents a very
promising opportunity for the product candidate."
Brain Metastases
It is estimated that as many as 20% of all patients with cancer
will develop brain metastases (secondary tumours in the central
nervous system). The most common primary tumours that spread to the
brain include lung, breast, colorectal, melanoma, and renal cell
carcinoma. Median overall survival for patients diagnosed with
brain metastases ranges from 2.3 to 7.7 months.[1] It is
estimated that approximately 200,000 patients are diagnosed with
brain metastases each year in the United
States alone.[2]
Radiotherapy is the mainstay of treatment for brain metastases,
and generally consists in either stereotactic radiosurgery (SRS) or
whole brain radiotherapy (WBRT) or some combination thereof. The
efficacy of WBRT differs according to the type of tumour and the
number and volume of brain metastases, but several recent
publications cite overall response rates of 20-45%.
Publication
|
Setting
|
ORR
|
Arrietta et al.
(2020)
|
NSCLC
|
47.1 %
|
Zhou et al.
(2021)
|
NSCLC
(meta-analysis)
|
20.4% -
27.4%
|
Kim et al.
(2020)
|
HER2+ breast
cancer
|
42 %
|
Clinical Study Rationale and Design
Research by Dr. Yang and others has shown that activation of the
PI3K pathway is common in brain metastases, even in some cases
where it is not present in the primary tumour. Moreover, PI3K
pathway activation appears to be induced by radiotherapy, and to
confer upon the tumour resistance to radiotherapy. These
observations provide a strong rationale for testing the combination
of a brain-penetrant PI3K inhibitor with radiotherapy.
This phase I study is a single-arm prospective trial comprising
patients with brain metastases or leptomeningeal metastases from
any primary tumour. The primary objective is safety and
tolerability. All patients have PI3K pathway mutations at baseline.
The first stage of the study is intended to establish the MTD of
paxalisib in combination with WBRT and to characterise safety and
tolerability. The second stage is intended to elicit confirmatory
signals of efficacy, with the intent to recruit a further 12
patients.
Next Steps
Enrolment to the second stage of the study is already underway
and we currently estimate preliminary data from the second part of
the phase I clinical trial in CY2023.
Kazia expects to discuss emerging data from this study, along
with other research in brain metastases, with its scientific
advisors and regulatory consultants in due course, with potential
FDA consultation at a future date.
Summary of Abstract
Session 2: Multimodality Approaches to Primary and Secondary
Brain Tumors - Invited
Speakers and Oral Abstracts
Friday, 12 August 2022
11am – 1pm
Abstract MMAP-05 - Phase I study of concurrent
paxalisib and radiation therapy in patients with solid tumor brain
metastases or leptomeningeal metastases harboring PI3K pathway
mutations: results from the dose-escalation cohort
(NCT04192981)
Lead Author: T Jonathan Yang, MD,
PhD
Institution: Memorial Sloan Kettering Cancer Center,
New York, NY
For More Information, Please Contact:-
In the United
States:
Joe Green
Edison Investor
Relations
jgreen@edisongroup.com
Phone: +1
646-653-7030
|
In
Australia:
Jane Lowe
IR
Department
jane.lowe@irdepartment.com.au
Phone: +61 411 117
774
|
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (NASDAQ: KZIA; ASX: KZA) is an
oncology-focused drug development company, based in Sydney, Australia.
Our lead program is paxalisib, a brain-penetrant 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 commenced recruitment to GBM AGILE, a pivotal study in
glioblastoma, in January 2021. Seven
additional studies are active in various 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, and for
AT/RT in June 2022.
Kazia is also developing EVT801, a small-molecule inhibitor of
VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to
be active against a broad range of tumour types and has provided
compelling evidence of synergy with immuno-oncology agents. A phase
I study commenced recruitment in November
2021.
For more information, please visit www.kaziatherapeutics.com or
follow us on Twitter @KaziaTx.
Forward-Looking Statements
This announcement may contain forward-looking statements, which
can generally be identified as such by the use of words such as
"may," "intend," "potential," "prospective," or other similar
words, and may include statements regarding the therapeutic
potential of Kazia's product candidates and anticipated results
from clinical trials. Kazia's product candidates may include
paxalisib, EVT801, or other molecules, administered alone or in
combination with other therapies for any disease. Any statement
describing Kazia's future plans, strategies, intentions,
expectations, objectives, goals or prospects, and other statements
that are not historical facts, are also forward-looking statements.
Such statements are based on Kazia's expectations and projections
about future events and future trends affecting our business and
are subject to certain risks and uncertainties that could cause
actual results to differ materially from those anticipated in the
forward-looking statements, including risks and uncertainties
associated with clinical trials and product development and the
impact of global economic conditions. These and other risks and
uncertainties, are described more fully in Kazia's Annual Report,
filed on form 20-F with the SEC, and in subsequent filings to SEC.
Kazia undertakes no obligation to publicly update any
forward-looking statement, whether as a result of new information,
future events, or otherwise, except as required under applicable
law. You should not place undue reliance on these forward-looking
statements, which apply only as of the date of this announcement.
Actual results could differ materially from those discussed in this
announcement.
This document was authorized for release to the ASX by
James Garner, Chief Executive
Officer, Managing Director.
[1] AS
Achrol et al. (2019) Nat Rev Disease Primers
5(5):1-26
|
[2] DA
Hardesty & P Nakaji (2016) Front Surg. 3(30)
|
Board of Directors
Mr Iain Ross Chairman,
Non-Executive Director
Mr Bryce Carmine
Non-Executive Director
Mr Steven Coffey
Non-Executive Director
Dr James Garner Chief
Executive Officer, Managing Director
Three International Towers, Level 24, 300 Barangaroo Avenue,
Sydney NSW 2000
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