VANCOUVER, British Columbia and
MENLO PARK, Calif., July 24, 2017 /PRNewswire/ -- DelMar
Pharmaceuticals (Nasdaq: DMPI) ("DelMar" and "the Company"), a
biopharmaceutical company focused on the development of new cancer
therapies, today announced that the Human Genetic Resources
Administration of China (HGRAC),
has approved the Company's application to initiate a Phase 2 safety
and efficacy study of its lead product candidate VAL-083 in newly
diagnosed MGMT-unmethylated glioblastoma multiforme (GBM). DelMar
was required to obtain HGRAC approval because the trial involves
analysis of patient's MGMT status as a biomarker for patient
selection and enrollment.
"Our clinical trials to date have been focused on recurrent GBM
for patients whose tumors have recurred following currently
approved therapies. Obtaining HGRAC approval represents a
significant step toward maximizing the potential benefit of VAL-083
in newly diagnosed GBM for patients whose tumors exhibit features,
such as high expression of MGMT, which render them resistant to the
current standard-of-care chemotherapy," said Jeffrey Bacha, Chief Executive Officer of DelMar
Pharmaceuticals. "Success of VAL-083 as a front-line treatment
would be a major turning point for the brain tumor community and
this area of science."
Up to 30 newly diagnosed GBM patients whose tumors exhibit
high-expression of the DNA-repair enzyme O6-methylguanine
methyltransferase (MGMT) will be treated with VAL-083 in
combination with radiotherapy to examine the safety and efficacy of
VAL-083 in this population. MGMT methylation status will be used as
a biomarker for patient selection and only patients whose tumors
are MGMT-unmethylated will be enrolled.
Results of the trial will be used to guide design of global
randomized trials, which if successful, would position VAL-083 as a
potential replacement for the current standard-of-care
(chemoradiation with temozolomide) for the approximately 2/3 of
newly diagnosed GBM patients whose tumors feature MGMT-unmethylated
GBM.
GBM patients with MGMT-unmethylated tumors exhibit a high
expression of the MGMT enzyme, which is directly correlated to
resistance to temozolomide, the current front-line chemotherapy
used in the treatment of GBM. MGMT-unmethylated patients have
particularly poor patient outcomes and significantly reduced
survival compared to MGMT-methylated patients.
DelMar has demonstrated that VAL-083's anti-cancer activity is
independent of MGMT expression against multiple GBM cell lines
in vitro. VAL-083's clinical activity against GBM has
been established by DelMar's recent Phase 2 clinical trials in
refractory GBM and historical trials conducted by the US National
Cancer Institute (NCI). Results of prior NCI-sponsored trials
of VAL-083 combined with radiotherapy in newly diagnosed GBM
suggest a potential superior benefit of chemoradiation with VAL-083
versus radiotherapy alone (+8.3 months) in comparison to similar
studies involving temozolomide or nitrosoureas (+1.2 – 2.5
months).
Mr. Bacha continued, "GBM has been largely left behind in the
recent advancements made in the fight against cancer and new
therapies improving median survival have been lacking. We
strongly believe that VAL-083 represents a potential paradigm shift
in the treatment of GBM, particularly for the 2/3 of newly
diagnosed GBM patients whose tumors exhibit high expression of
MGMT."
The trial is expected to open for enrollment in the coming weeks
at Sun Yat-sen University Cancer Center (SYUCC) in Guangzhou, China under the direction of
Professor Zhong-ping Chen, M.D., Ph.D., who serves as chair of the
Department of NeuroSurgery/Neuro-Oncology at SYUCC. Prof. Chen
has authored dozens of publications and been involved in numerous
international brain tumor trials. He also currently serves as
president of the Chinese Society for NeuroOncology and as
editor-in-chief of the Chinese Journal of NeuroOncology. Kun
Tuo, a subsidiary of QuintilesIMS, has been retained to monitor and
oversee the conduct of the trial. Funding support for the
trial will be provided by Guangxi Wuzhou Pharmaceutical Group Co.
Ltd. (Guangxi Wuzhou Pharma), under the terms of DelMar's
collaboration with Guangxi Wuzhou Pharma. Further details of
the trial can be found at clinicaltrials.gov (Identifier Number:
NCT03050736)
About VAL-083
VAL-083 (dianhydrogalactitol) is a "first-in-class",
DNA-targeting agent that introduces interstrand DNA cross-links at
the N7-position of guanine leading to DNA double-strand breaks and
cancer cell death. VAL-083 has demonstrated clinical activity
against a range of cancers including GBM in historical clinical
trials sponsored by the U.S. National Cancer Institute.
VAL-083 has been granted an orphan drug designation by the U.S.
FDA Office of Orphan Products for the treatment of glioma,
medulloblastoma and ovarian cancer, and in Europe for the treatment of malignant
gliomas.
DelMar has demonstrated that VAL-083's anti-tumor activity
against GBM is unaffected by the expression of MGMT in
vitro. Further details regarding these studies can be
found
at http://www.delmarpharma.com/scientific-publications.html.
The Company's recent outcomes in Phase 1-2 clinical trials
suggest that VAL-083 may offer a clinically meaningful survival
benefit for patients with recurrent GBM following treatment with
both TMZ and bevacizumab. A well-tolerated dosing regimen of
40mg/m2/day on days 1, 2, and 3 of a 21-day cycle was
selected for study in subsequent GBM clinical trials.
Based on these results, DelMar has embarked on human clinical
trials for VAL-083 across multiple lines of GBM therapy. These
trials include, i) an ongoing single-arm, biomarker driven, Phase 2
study to determine if VAL-083 treatment
of MGMT-unmethylated adult GBM patients at first
recurrence/progression, prior to bevacizumab, improves overall
survival, compared to historical control with
lomustine (clinicaltrials.gov identifier: NCT02717962);
ii) a pivotal, controlled Phase 3 study in temozolomide-Avastin
Recurrent GBM ("STAR-3") to evaluate overall survival versus
salvage chemotherapy (clinicaltrials.gov identifier:
NCT03149575); and iii) a single arm, biomarker driven,
Phase 2 study to confirm the tolerability and efficacy of VAL-083
in combination with radiotherapy in newly
diagnosed MGMT-unmethylated GBM patients whose tumors
are known to express high MGMT levels (clinicaltrials.gov
identifier: NCT03050736). DelMar believes that the results of
these studies may support a new treatment paradigm in
chemotherapeutic regimens for the treatment of GBM.
About Glioblastoma Multiforme (GBM)
Glioblastoma multiforme (GBM) is the most common and aggressive
primary brain cancer. GBM has an incidence of two to three per
100,000 adults per year, and accounts for 52 percent of all primary
brain tumors. In the US alone, approximately 18,000 people are
diagnosed with GBM every year. GBM accounts for 13,000 cancer
deaths in the US annually. Current standard of care includes
surgery, radiation and treatment with temozolomide (TMZ), however
nearly all tumors recur and the prognosis for recurrent GBM is
dismal. Most GBM tumors have unmethylated promoter status for
O6-methylguanine-DNA-methyltransferase (MGMT); a validated
biomarker for TMZ-resistance. Second-line treatment with
anti-angiogenic agent bevacizumab has not improved overall survival
(OS) and 5-year survival is less than 3%.
About DelMar Pharmaceuticals, Inc.
DelMar Pharmaceuticals, Inc. is developing cancer therapies in
indications where patients are failing or have become intolerable
to modern targeted or biologic treatments. The Company's pipeline
is based around VAL-083, a "first-in-class," small-molecule
chemotherapeutic with a novel mechanism of action that has
demonstrated clinical activity against a range of cancers including
glioblastoma multiforme (GBM), ovarian and other solid tumors (e.g.
NSCLC, bladder cancer, head & neck) in U.S. clinical trials
sponsored by the National Cancer Institute (NCI). VAL-083 has been
granted an orphan drug designation by the U.S. FDA Office of Orphan
Products for the treatment of glioma, medulloblastoma and ovarian
cancer, and in Europe for the
treatment of malignant glioma.
For further information, please visit http://delmarpharma.com/;
or contact DelMar Pharmaceuticals Investor Relations:
ir@delmarpharma.com / (604) 629-5989. Media Contact: Fisctank
PR (646) 699-1148
Connect with the DelMar Pharmaceuticals on Twitter, LinkedIn,
Facebook, and Google+.
Safe Harbor Statement
Any statements contained in this press release that do not
describe historical facts may constitute forward-looking statements
as that term is defined in the Private Securities Litigation Reform
Act of 1995. Any forward-looking statements contained herein are
based on current expectations, but are subject to a number of risks
and uncertainties. The factors that could cause actual future
results to differ materially from current expectations include, but
are not limited to, risks and uncertainties relating to the
Company's ability to develop, market and sell products based on its
technology; the expected benefits and efficacy of the Company's
products and technology; the availability of substantial additional
funding for the Company to continue its operations and to conduct
research and development, clinical studies and future product
commercialization; and, the Company's business, research, product
development, regulatory approval, marketing and distribution plans
and strategies. These and other factors are identified and
described in more detail in our filings with the SEC, including,
our current reports on Form 8-K.
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