GBM AGILE trial data shows clinically meaningful
improvement in a prespecified secondary analysis for overall
survival in paxalisib-treated, newly diagnosed unmethylated
patients with glioblastoma
SYDNEY, July 10,
2024 /PRNewswire/ -- Kazia Therapeutics Limited
(NASDAQ: KZIA), an oncology-focused drug development company, is
pleased to announce results from GBM-AGILE, a phase II/III study
that included an evaluation of paxalisib versus standard of care
(SOC) for patients with glioblastoma (NCT03522298), a
life-threatening brain cancer, where there is an urgent unmet need
for new therapeutics.
GBM AGILE STUDY
GBM AGILE is an adaptive phase II/III
global trial sponsored by the Global Coalition for Adaptive
Research (GCAR), a nonprofit organization comprised of some of the
world's foremost clinical, translational, and basic science
researchers, from institutions such as Memorial Sloan Kettering
Cancer Center and Dana-Farber Cancer Institute. The trial is
designed to efficiently screen for and characterize the response of
glioblastoma (GBM) patients to novel investigative agents.
Utilizing a complex innovative design, Bayesian principles are
applied to the primary endpoint (Overall Survival) comparison of
the investigational agents to patients receiving Standard of Care
(SOC) enrolled from the study start (also referred to as cumulative
control population). In general, secondary analyses and
endpoints are assessed based on established statistical models in
comparison to the control patients enrolled at the same time as the
investigational agent (concurrent control population).
Paxalisib is the third drug candidate to complete its evaluation
in the study and was evaluated in newly diagnosed glioblastoma
patients with unmethylated MGMT promoter status as well as in
patients with recurrent disease.
GBM AGILE Paxalisib Results
Kazia CEO, Dr John Friend stated,
"We are excited to have shown a 3.8 month improvement in overall
survival, an approximate 33% improvement, for newly diagnosed
unmethylated patients with GBM compared to the concurrent standard
of care arm. Having comparable Overall Survival data across two
independent studies is a compelling outcome in this difficult to
treat glioblastoma population. We look forward to discussing
possible approaches for an accelerated approval pathway for
paxalisib with the FDA."
A total of 313 newly diagnosed unmethylated (NDU) patients and
recurrent patients being treated at top US cancer hospitals were
randomized in Stage 1 to either a paxalisib treatment arm (60
mg/day) or the SOC concurrent control arm from January 2021 to May 2022. The cumulative
control arm was enrolled from July
2019 (GBM Agile study start date) to May 2022.
For the primary analysis the median Overall Survival (OS) was
14.77 months for paxalisib-treated NDU patients (n=54) versus 13.84
months for cumulative SOC NDU patients (n=75).
For a prespecified secondary analysis in the NDU patients,
median OS was 15.54 months in the paxalisib arm (n=54) versus 11.89
months for concurrent SOC (n=46). In addition, a prespecified
sensitivity analysis in NDU patients showed similar median OS
difference between paxalisib treated patients (15.54 months) and
concurrent SOC patients (11.70 months).
The secondary analysis results are consistent with the
previously reported Company-sponsored phase II study, where median
OS was 15.7 months (n=27) for paxalisib treated NDU patients
compared to 12.7 months historically reported with temozolomide in
this patient group (Wen 2022).
Paxalisib was well tolerated in GBM-AGILE, and no new safety
signals were identified in this patient population.
An efficacy signal was not detected in the recurrent disease
population (median OS of 9.69 months for concurrent SOC (n=113)
versus 8.05 months for paxalisib (n=100). Similar results in this
population have been reported in the other two drug candidates that
have completed the GBM AGILE trial. Kazia is currently pursuing
further analyses of this data to elucidate potential signals for
further consideration.
Based on the totality of data available from all completed
paxalisib clinical studies in newly diagnosed unmethylated GBM
patients, Kazia will request a meeting with the US Food & Drug
Administration (FDA) to discuss the results and determine if a
potential path to accelerated approval is appropriate for
paxalisib.
Paxalisib has previously received orphan drug designation and
fast track designation from the FDA for glioblastoma in
unmethylated MGMT promoter status patients, following radiation
plus temozolomide therapy.
Full data including secondary endpoints from the paxalisib arm
of the GBM AGILE study is expected to be presented at a scientific
meeting later this year.
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, has been
completed with presentation of paxalisib arm data expected later in
2024 at a major medical conference. Other clinical trials involving
paxalisib are ongoing in brain metastases, diffuse midline gliomas,
and primary CNS lymphoma, with several of these trials having
reported encouraging interim data.
Paxalisib was granted Orphan Drug Designation for glioblastoma
by the 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 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 presentation of preliminary data at a medical
conference is anticipated in CY2024.
For more information, please visit www.kaziatherapeutics.com or
follow us on X @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, the potential benefits of Kazia's product
candidates, including paxalisib, 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