SYDNEY, Nov. 1, 2023
/PRNewswire/ -- Kazia Therapeutics Limited (NASDAQ: KZIA; ASX:
KZA), an oncology-focused drug development company, is pleased to
provide a preliminary update from the ongoing
investigator-initiated Phase 2 clinical trial (NCT04906096)
evaluating paxalisib as monotherapy treatment in patients with
relapsed/refractory primary central nervous system lymphoma (r/r
PCNSL).
This is an open-label, Phase 2 clinical trial, led by Dr.
Lakshmi Nayak MD, of the Dana-Farber Cancer Institute in
Boston, MA. Eligible
patients with r/r PCNSL will be administered paxalisib as
monotherapy for up to 24 months, in an initial dosing regimen of
60mg daily, which is similar to the dosing regimen used for
paxalisib clinical trials in other adult brain cancers. The
objectives of the study are to assess the clinical efficacy and
safety of paxalisib in up to twenty-five (25) patients with r/r
PCNSL based on objective response rate (ORR), duration of response
(DOR), progression-free survival (PFS) and overall survival
(OS). To date, fourteen (14) patients have been enrolled in
the study.
Clinical activity has been preliminarily observed in enrolled
patients, including partial responses and stable disease. Although
early clinical activity was observed in some patients, several
heavily pretreated r/r PCNSL patients experienced treatment-related
adverse events consistent with those previously reported with
paxalisib, that resulted in dose reductions and, in some cases,
early termination from the study. As such, the protocol is
being optimized by the investigator to initiate starting doses at
15mg twice a day or 30mg once a day with the goal of improving the
durability of clinical benefit and overall tolerability.
"We are encouraged by the clinical activity preliminarily
observed to date and agree with the lead investigator to reduce the
dose with the goal of improving tolerability and durability of
response," stated Dr. John Friend,
CEO Kazia Therapeutics. "The
investigator has enrolled over half the patients needed to complete
this study, and we look forward to receiving additional clinical
updates in the future."
Primary CNS Lymphoma
Primary central nervous system lymphoma (PCNSL) is a rare, poor
prognosis subtype of extranodal, non-Hodgkin's lymphoma (NHL),
which accounts for 4% of primary brain tumours. Approximately 90%
of PCNSL cases are diffuse large-B cell lymphoma (DLBCL) in origin,
with T-cell lymphoma, Burkitt's lymphoma and poorly characterized
low-grade lymphoma representing a much smaller percentage of
disease.
Despite an aggressive approach to the initial treatment
involving high-dose methotrexate-based chemotherapy, whole-brain
radiotherapy (WBRT) and autologous stem cell transplantation
(ASCT), nearly 50% of patients recur after two years, with a third
of patients becoming refractory early in the course of
treatment.
Optimal therapy in the setting of either recurrence or
treatment-refractoriness has not yet been established and most
patients ultimately die of their disease, underscoring the fact
that PCNSL remains a major unmet need in oncology today. The
treatment of r/r PCNSL has largely been based on the experience
gathered in numerous small retrospective studies and a limited
number of prospective clinical trials. The clinical evidence from
these approaches have demonstrated limited efficacy and
durability.
Lymphoma outside the CNS has been a successful 'use case' for
PI3K inhibitors, with four of the five FDA-approved therapies
indicated for some form of the disease. There is a rationale for a
brain-penetrant agent to examine CNS lymphoma, which is otherwise
relatively treatment resistant to existing therapies.
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, 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 CY2023. 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 US Food and Drug Administration (FDA) in February 2018, and Fast Track Designation (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 harbouring 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 (AT/RT) 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
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," "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 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, related to
Kazia's executive leadership changes, 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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