Paxalisib plus Radiotherapy Data Shows
Promise for Treating Patients with PI3K Pathway Mutation Brain
Metastases
SYDNEY, Feb. 21,
2024 /PRNewswire/ -- Kazia Therapeutics Limited
(NASDAQ: KZIA), a biotechnology company specializing in oncology,
today announced the early conclusion based on positive safety and
promising clinical response findings observed to date of an
important two-part Phase I trial. This investigator-initiated trial
evaluated the use of paxalisib (an oral PI3K/mTOR dual inhibitor)
with radiation therapy for the treatment of patients with PI3K
pathway mutation brain metastases from solid tumors.
Part I of the study established the maximal tolerated dose (MTD)
of paxalisib in combination with radiation therapy, while also
demonstrating promising signs of clinical activity in all nine
evaluable patients. Part II was a follow-on expansion cohort to
further evaluate safety and efficacy of the MTD (45mg daily)
combined with radiation therapy in up to 12 additional
patients.
After reviewing the Part II patient data generated to date, the
three lead investigators have determined that the primary endpoint
of the study has been reached. In addition, the investigators
continued to observe encouraging signs of clinical response in
patients in the expansion cohort. Detailed findings from Part II of
this study are slated for submission and presentation at a
forthcoming global scientific meeting, where they will contribute
to the ongoing conversation about treatment options for patients
with these complex brain metastases.
Kazia's CEO, Dr. John Friend,
shared his enthusiasm: "We are extremely excited about these
findings, which include not only encouraging safety data but also
some promising efficacy signals for paxalisib in combination with
radiation therapy. We are now preparing to engage with the Food and
Drug Administration to discuss the data and seek guidance on the
conduct of a pivotal registration study, with the goal of rapidly
progressing paxalisib's development to potentially provide a more
effective treatment option for patients with brain metastases."
Previous research by Dr. Jonathan
Yang, Director of Metastatic Disease and Developmental
Therapeutics, Department of Radiation Oncology, University of Washington School of Medicine, and
others, has shown that activation of the PI3K pathway is common in
brain metastases. Moreover, PI3K pathway activation appears to
result in tumor resistance to radiotherapy, which supports the
rationale for evaluating paxalisib with radiotherapy in order to
potentially sensitize the tumor cells to radiotherapy and achieve
better disease control. Dr. Yang presented the Part I data at the
2022 Annual Conference on CNS Clinical Trials and Brain Metastases,
jointly organized by the Society for Neuro-Oncology and the
American Society for Clinical Oncology, held in Toronto, Canada.
Last year, paxalisib was awarded Fast Track Designation (FTD) on
the basis of the Part I clinical data by the United States Food and
Drug Administration (FDA) for the treatment of solid tumor brain
metastases harboring PI3K pathway mutations in combination with
radiation therapy.
Approximately 200,000 cancer patients develop brain metastases
in the United States each year.
Radiotherapy is the mainstay of treatment for brain metastases, and
generally consists of either stereotactic radiosurgery (SRS) or
whole brain radiotherapy (WBRT) or some combination thereof. The
efficacy in patients who receive WBRT differs according to the type
of tumor and the number and volume of brain metastases, but several
recent publications cite overall response rates of 20-45%. The
increasing incidence of brain metastasis and the low response rates
to existing treatments underscores the need for new treatment
options.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused
drug development company, based in Sydney, Australia.
Our lead program is paxalisib, an investigational
brain-penetrant inhibitor of the PI3K / Akt / mTOR pathway, which
is being developed to treat multiple forms of brain cancer.
Licensed from Genentech in late 2016, paxalisib is or has been the
subject of ten clinical trials in this disease. A completed Phase 2
study in glioblastoma reported early signals of clinical activity
in 2021, and a pivotal study in glioblastoma, GBM AGILE, is
ongoing, with final data expected in 1H2024. Other clinical trials
are ongoing in brain metastases, diffuse midline gliomas, and
primary CNS lymphoma, with several of these having reported
encouraging interim data.
Paxalisib was granted Orphan Drug Designation for glioblastoma
by the FDA in February 2018, and FTD
for glioblastoma by the FDA in August
2020. Paxalisib was also granted FTD in July 2023 for the treatment of solid tumour brain
metastases harboring PI3K pathway mutations in combination with
radiation therapy. In addition, paxalisib was granted Rare
Pediatric Disease Designation and Orphan Drug Designation by the
FDA for diffuse intrinsic pontine glioma in August 2020, and for atypical teratoid / rhabdoid
tumours in June 2022 and July 2022, respectively.
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
evidence of synergy with immuno-oncology agents. A Phase I study is
ongoing and preliminary data is anticipated in CY2024.
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," "will," "estimate," "future," "forward," "anticipate," or
other similar words. 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, including, but not limited to,
statements regarding: the timing for results and data related to
Kazia's clinical and preclinical trials and investigator-initiated
trials of Kazia's product candidates, and Kazia's strategy and
plans with respect to its programs, including paxalisib and EVT801.
Such statements are based on Kazia's current expectations and
projections about future events and future trends affecting its
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 and preclinical trials and
product development, related to regulatory approvals, and related
to 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 United States Securities and
Exchange Commission (SEC), and in subsequent filings with the 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.
This announcement was authorized for release by Dr John Friend, CEO.
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SOURCE Kazia Therapeutics Limited