SYDNEY, Nov. 17, 2020 /PRNewswire/ -- Kazia Therapeutics
Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused
biotechnology company, is pleased to share a summary of new
paxalisib data presented at the Society for Neuro-Oncology (SNO)
Annual Meeting, which is being held virtually from 19-21 November 2020.
Key Points
- New interim analysis of paxalisib phase II study in
glioblastoma (NCT03522298) is highly consistent with prior
data
- Median progression-free survival (PFS) of 8.4 months reported
on this analysis (versus 5.3 months for temozolomide, the existing
standard of care)
- Median overall survival (OS) of 17.5 months reported (versus
12.7 months for temozolomide)
- First substantial presentation of safety data at a 60mg dose
shows profile very similar to prior experience, with the most
common toxicities including rash, stomatitis (mouth ulcers), and
hyperglycemia (high blood sugar), consistent with other PI3K and
mTOR inhibitors
- Phase I study in DIPG (NCT03696355) shows paediatric maximum
tolerated dose (MTD) of 27 mg/m2, with safety profile
and pharmacokinetics similar to adult data
Kazia CEO, Dr James Garner,
commented, "this is very reassuring data from the glioblastoma
study, confirming our earlier results with the data now much more
mature. In studies such as this, volatility is the enemy of
dependability. From the very first efficacy data we reported from
this study, in November 2019, through
the ASCO and AACR presentations in June
2020, to today's latest analysis, the PFS and OS figures
have remained extremely stable as the study has progressed. This
gives us a great deal of confidence that what we are seeing is
representative and reliable."
He added, "we expect this study to conclude in the first half of
calendar 2021, but it has already provided useful information to
guide the development of paxalisib. We have moved into the
operational phase of the GBM AGILE pivotal study, and we expect
that study to now be the primary focus of our work in glioblastoma
from this point forward."
The poster presentation is available for download via the Kazia
website at:-
https://www.kaziatherapeutics.com/researchpipeline/paxalisib
Summary of Paxalisib Data in Comparison to Temozolomide
(existing standard of care)
|
Temozolomide[1]
(FDA-approved treatment)
|
Paxalisib
(interim phase II
data)
|
Progression-Free
Survival (PFS)
|
5.3 months
|
8.4 months
|
Overall Survival
(OS)
|
12.7
months
|
17.5
months
|
Professor Patrick Wen, the first
author on the poster, commented "as this study has matured, we have
seen encouraging results that are very stable over successive
analyses, and very consistent with prior clinical experience in
this drug. Paxalisib is now moving into the GBM AGILE study in
glioblastoma, and we expect this to provide definitive data
regarding the drug's potential use in this disease and, if
successful, a basis for regulatory approval. There remains a
profound need for new treatments in glioblastoma, and paxalisib has
proven to be an exciting potential candidate."
Initial Data from St Jude Study of Paxalisib in DIPG and
Diffuse Midline Gliomas
Dr Christopher Tinkle, lead
investigator for the SJPI3K study of paxalisib in DIPG and diffuse
midline glioma (NCT03696355), gave an invited oral presentation on
interim results from that study.
The SJPI3K study is a first-in-paediatric study, designed to
establish the safety and pharmacokinetics of paxalisib in children,
and to explore potential early signals of efficacy in this patient
population.
The study recruited 27 patients, ranging from 3 to 16 years of
age. Four patients discontinued participation prior to receiving a
first dose of paxalisib, generally due to disease progression. At
the time of analysis, five patients remain on paxalisib treatment,
and several patients remain in post-treatment follow-up.
The paediatric maximum tolerated dose (MTD) was determined to be
27 mg/m2. The dose-limiting toxicities (DLTs) included
hyperglycaemia, oral mucositis, and rash, which are entirely
consistent with the adult experience.
The pharmacokinetics of the drug, a term which describes the
concentration of the drug in plasma over time, was very consistent
with the adult experience. The study found no meaningful difference
between administration of intact capsules and administration via
opening of capsules and sprinkling of contents onto a food
carrier.
The study has not at this stage shown a clear survival benefit
for paxalisib in comparison to historical controls. In terms of
PFS, the proportion of patients alive and progression-free at six
months (PFS6) was 96%, which compares favourably to an historical
control of 58%[2]. However, the authors note that PFS can be a
complex endpoint to interpret in DIPG trials due to the confounding
effect of incidental radiological changes associated with radiation
therapy.
Dr Tinkle commented, "my colleagues and I are very pleased with
the outcome of this study. We have determined an appropriate dose
for future paediatric work, established an acceptable tolerability
profile in children, and demonstrated pharmacokinetic equivalence
between intact capsule and open and sprinkled administration, which
are critical steps in the development of any new drug for
paediatric cancer."
He added, "DIPG is an extremely treatment-resistant disease, and
no drug has ever shown convincing efficacy as a monotherapy. Our
view has always been that the treatment of this disease will
consist in combination therapy, and we have shown that paxalisib is
eminently suitable to now be evaluated alongside other agents. We
look forward to discussing follow-on work that will explore these
opportunities and further investigate paxalisib's potential."
Dr Garner commented, "we are grateful to have had the
opportunity to collaborate with one of the world's leading
paediatric oncology hospitals in this study. The results provide an
excellent foundation for the further development of paxalisib in
DIPG, and we will be excited to discuss the next phase of work with
our collaborators in coming months."
Next Steps
The paxalisib phase II study remains ongoing, with final data
expected in 1H CY2021. The paxalisib arm of the GBM AGILE study has
moved into an operational phase, and first patient in is expected
early in 1Q CY2021.
The St Jude study in DIPG remains ongoing, with final data
expected during 1H CY2021.
Investor Conference Call
Kazia is pleased to invite investors to attend a conference call
to discuss the results further.
The call will be held on Thursday 19
November 2020 at 12:00pm,
Sydney time (AEDT), which is
5pm on Wednesday 18 November 2020 in San
Francisco (PST) and 8pm on
Wednesday 18 November 2020 in
New York (EST).
Participants will need to pre-register for the call via
the following link:
https://s1.c-conf.com/diamondpass/10011029-8iqiBr.html
Click the 'Register Now' button and follow the prompts to
complete pre-registration. You will then receive a calendar invite
with dial in numbers, a passcode and a PIN to dial into the
conference call.
[1] ME Hegi, A-C Desirens, T Gorlia, et al. N Engl J
Med (2005); 352:997-1003
[2] T Cooney, A Lane, U Bartels, et al.
Neuro-Oncology (2017); 19(9):1279-1280
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SOURCE Kazia Therapeutics Ltd