SYDNEY, Dec. 4, 2021 /PRNewswire/ -- Kazia
Therapeutics Limited (NASDAQ: KZIA; ASX: KZA), an oncology-focused
drug development company, is pleased to announce positive final
data from a phase II clinical study of paxalisib as first line
therapy in patients with glioblastoma (NCT03522298). The results
confirm the previously reported safety and efficacy profile with
paxalisib in this high unmet need disease.
Key Points
- The study recruited 30 patients with newly diagnosed
glioblastoma and unmethylated MGMT promotor status, a genetic
profile which confers primary resistance to temozolomide, the only
existing FDA-approved drug treatment for first line treatment.
- 60mg once daily was identified as the maximum tolerated dose
(MTD) and selected for future studies.
- Median overall survival (OS) in the intent-to-treat (ITT)
population (n=30) was 15.7 months (11.1 – 19.1), which compares
very favourably to 12.7 months historically reported with
temozolomide in this patient group.1
- Median progression-free survival (PFS) in the ITT population
was 8.4 months (6.6 – 10.2), representing a substantial increment
over the comparable figure of 5.3 months associated with
temozolomide.
- In the modified ITT (mITT) population (n=27), which includes
only those patients evaluable for efficacy, OS increased to 15.9
months (12.8 – 19.1).
- The safety profile of paxalisib was highly consistent with
previous clinical studies: hyperglycaemia, oral mucositis, and skin
rash were among the most common drug-related toxicities.
- Kazia expects to receive a final clinical study report in 1Q
CY2022 and intends to seek publication of these data in a
peer-reviewed scientific journal thereafter.
Kazia CEO, Dr James Garner,
commented, "We are delighted to report positive final data from the
completed phase II study of paxalisib. The data continue to
demonstrate a clear efficacy signal and favourable safety profile,
suggesting a meaningful advantage over temozolomide, the existing
standard of care, and validating our decision last year to join the
GBM AGILE pivotal study. We have gleaned invaluable insights from
this trial, and we are tremendously grateful to the investigators
and to the patients who participated. Our task now, as we move
rapidly toward a potential marketing authorization, is to confirm
and quantify the benefit associated with paxalisib in glioblastoma
patients. This indeed is the focus of our participation in GBM
AGILE, which commenced recruiting to the paxalisib arm in
January 2021. We are increasingly
also exploring additional patient populations for which a brain
penetrant PI3K/mTOR inhibitor may provide significant advantages
over the standard of care."
Professor Patrick Wen, Principal
Investigator at Dana Farber Cancer Institute, commented "We are
pleased to see the phase II study of paxalisib successfully
completed. This data supports the inclusion of paxalisib in the GBM
AGILE study, which has recently expanded to Canada. Glioblastoma remains a disease in
urgent need of new therapeutic options, and we look forward to
seeing further data for paxalisib from GBM AGILE in due
course."
Clinical Trial Design
The phase II study of paxalisib was an adaptive trial, conducted
in two stages. The first stage sought to determine the most
appropriate dose in newly diagnosed patients. The second stage was
intended to provide additional information on dosing and to seek a
preliminary efficacy signal in order to de-risk transition to a
larger, pivotal study.
Consistent with these objectives, the primary objective of the
study was to evaluate the safety and tolerability of paxalisib in
patients with newly diagnosed glioblastoma. The secondary
objectives included typical pharmacokinetic parameters, and
efficacy endpoints including overall survival (OS) and
progression-free survival (PFS).
The phase II study was conducted in 30 patients at six centres
in the United States. It was a
single arm study in which all patients received paxalisib as a
monotherapy. As such, all data must be interpreted in the context
of historical comparators. Specifically, Kazia has referred to the
pivotal study of temozolomide, the only existing FDA-approved drug
for this patient population. Such comparisons are always inexact,
and this study was not designed either to precisely quantify the
benefit associated with paxalisib or to demonstrate statistical
significance. Rather, these are among the objectives of the ongoing
GBM AGILE pivotal trial.
Next Steps
On the basis of earlier interim analyses of this study, Kazia
made the decision in 4Q CY2020 to commence participation in the GBM
AGILE pivotal study. This global trial recruited its first patient
to the paxalisib arm in January 2021
and recruitment is ongoing. Kazia provisionally expects indicative
data in CY2023.
Seven other studies of paxalisib are ongoing in other forms of
primary brain cancer and in various forms of cancer that has
metastasized to the brain. The company is working with
investigators to crystalise the timing of initial data read-outs
from these studies. Kazia had expected at least two further
read-outs by the end of CY2021. Clinicians have now indicated that
data early in CY2022 is most likely. The company will continue to
keep shareholders closely informed as it receives further feedback
from investigators.
Having successfully concluded the phase II study in
glioblastoma, the investigators are composing a manuscript for
submission and publication to a peer-reviewed academic journal in
2022. Once the data has been more thoroughly analysed, Kazia
expects to share further detail with investors as it becomes
available.
1 ME Hegi et al. (2005) N Engl J Med.
352:997-1003
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SOURCE Kazia Therapeutics Ltd