SYDNEY, April 1, 2019 /PRNewswire/ -- Kazia Therapeutics
Limited (ASX: KZA; NASDAQ: KZIA), an Australian oncology-focused
biotechnology company, is pleased to provide investors with a
poster presentation summarising data from Part A of the ongoing
phase I study of Cantrixil (TRX-E-002-1) in ovarian cancer. The
poster will be presented at the American Association of Cancer
Research (AACR) Annual Meeting in Atlanta, GA at 1:00pm
EST on Monday 1 April 2019.
The poster number is CT019 and is available for download from the
Company's website.
Dr James Garner, Chief Executive
Officer of Kazia Therapeutics commented, "we are delighted to be
able to share positive results from the first part of the Cantrixil
phase I study in ovarian cancer, and it is very encouraging to have
been selected to do so at a conference as prestigious as AACR."
Key Points
- Part A of the study was performed at five sites in the United States and Australia. Fourteen patients were enrolled in
total, of which eleven received at least one dose of Cantrixil
- A Maximum Tolerated Dose (MTD) of 5mg/kg was determined. This
is well within the predicted therapeutic range, based on
preclinical data, and supports moving forward with subsequent
clinical development
- Of nine patients evaluable for efficacy, five (56%) achieved
stable disease after two cycles of Cantrixil monotherapy. One of
these five patients subsequently achieved a partial response when
Cantrixil was administered with chemotherapy, as intended per
protocol
- Main side effects were gastrointestinal in nature, with
abdominal pain and fatigue being the most common drug-related
observations, although not generally dose-limiting
- An expansion cohort is currently underway to seek efficacy
signals, and is planned to enroll 12 patients, all of whom will
receive a dose of 5 mg/kg; initial data from this cohort is
expected in 2H of calendar 2019
Dr Garner continued, "phase I studies are always primarily
safety studies. The data from this study shows that Cantrixil has a
safety profile very suitable for further development, and we
have been able to reach a dose well within the predicted
therapeutic range. It is extremely positive that we have seen some
preliminary evidence of efficacy at this early stage in
development, and the ongoing Part B of the study should give us
much more information."
The AACR Annual Meeting is one of the largest and most
prestigious cancer research meetings in the world. Clinical trial
abstracts are selected for presentation if they contain impactful
new data with the potential to influence treatment practice. The
conference brings together more than 20,000 representatives from
academia, industry, government and advocacy organisations from
across the globe.
The phase I study of Cantrixil commenced in December 2016 and is registered on
clinicaltrials.gov as NCT02903771. It is structured in two parts:
Part A aimed to understand the safety profile of Cantrixil and to
establish the Maximum Tolerated Dose (MTD), while Part B will
recruit 12 patients at the MTD to seek preliminary signals of
efficacy. Recruitment to Part B remains ongoing, and Kazia expects
to report initial data from this component of the study in the
second half of calendar 2019.
Following the recent opening of an additional site, the study is
currently being conducted at six hospitals in the United States and Australia:
Site
|
Principal
Investigator
|
United
States
|
|
Lifespan Cancer
Institute, Providence, RI
|
Dr. Don
Dizon
|
Stephenson Cancer
Center, Oklahoma City , OK
|
Assoc. Prof. Kathleen
Moore
|
Mary Crowley Cancer
Research Centre, Dallas, TX
|
Dr. Minal
Barve
|
Australia
|
|
ICON Cancer Care,
Brisbane, QLD
|
Assoc. Prof. Jermaine
Coward
|
Westmead Hospital,
Sydney, NSW
|
Prof. Paul
Harnett
|
Flinders Medical
Centre, Adelaide, SA
|
Dr. Ganessan
Kichenadasse
|
Daniel Berg, Clinical Program
Director for Cantrixil, commented, "we are fortunate to be working
with some of the leading specialists in this disease area. Ovarian
cancer remains a disease with significant unmet clinical need, and
we believe Cantrixil may represent an important addition to
therapeutic protocols."
The study protocol was designed such that patients received two
cycles (six weeks) of therapy with Cantrixil alone, followed by up
to six cycles (eighteen weeks) of Cantrixil administered in
combination with standard-of-care chemotherapy. In total, 14
patients were enrolled in Part A. However, three patients were
withdrawn before receiving a first dose of Cantrixil due to rapid
disease progression or other aspects of their pre-existing
condition, leaving 11 patients evaluable for safety. Of these, nine
patients completed the first cycle of treatment with Cantrixil,
making them evaluable for determination of the MTD.
The study enrolled patients at doses ranging from 0.24 mg/kg to
20 mg/kg, and 5 mg/kg was determined to be the maximum tolerated
dose. This is within the therapeutic range that would be predicted
from preclinical data. The main adverse events were
gastrointestinal in nature, and included abdominal pain, ileus, and
bowel obstruction. Diarrhoea, nausea, and vomiting were also seen,
but were not generally dose-limiting.
All patients had recurrent or persistent ovarian cancer and had
failed at least two prior lines of therapy, including platinum
therapy, prior to study entry, representing a very advanced
population. After two cycles of treatment with Cantrixil, five of
nine evaluable patients (56%) achieved stable disease, according to
the industry-standard RECIST criteria, which means that the tumour
remained approximately the same size over time and had not
progressed. One of these patients subsequently achieved a partial
response when Cantrixil was administered with standard-of-care
chemotherapy, which means that the tumour was reduced in size by
30% or more.
Four out of nine patients (44%) remained on study drug for the
entire 24-week duration of the study (approximately six months),
without experiencing progression of their disease. For comparison,
data from other studies in a similar patient group has found a
progression-free survival of approximately 3.4 to 4.7 months. This
further suggests the possibility that Cantrixil may help to delay
disease progression.
Ovarian cancer is diagnosed in approximately 240,000 women each
year worldwide and is the eighth most common cause of cancer death
in women. Conventional treatment typically includes surgery,
radiotherapy, and chemotherapy. However, the five-year survival
rate remains low, at approximately 45%, reflecting the fact that
the disease is often advanced at the time of diagnosis.
About Kazia Therapeutics Limited
Kazia Therapeutics Limited (ASX: KZA, NASDAQ: KZIA) is an
innovative oncology-focused biotechnology company, based in
Sydney, Australia. Our pipeline
includes two clinical-stage drug development candidates, and we are
working to develop therapies across a range of oncology
indications.
Our lead program is GDC-0084, a small molecule inhibitor of the
PI3K / AKT / mTOR pathway, which is being developed to treat
glioblastoma multiforme, the most common and most aggressive form
of primary brain cancer in adults. Licensed from Genentech in late
2016, GDC0084 entered a phase II clinical trial in March 2018. Initial data is expected in early
calendar 2019. GDC-0084 was granted orphan designation for
glioblastoma by the US FDA in February
2018.
TRX-E-002-1 (Cantrixil), is a third-generation benzopyran
molecule with activity against cancer stem cells, and is being
developed to treat ovarian cancer. TRX-E-002-1 is currently
undergoing a phase I clinical trial in Australia and the
United States. Initial data was presented in June 2018 and the study remains ongoing.
Cantrixil was granted orphan designation for ovarian cancer by the
US FDA in April 2015.
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