Biomarker-driven clinical trial will explore safety and efficacy of chemoradiation with VAL-083 as an alternative to standard-of-care temozolomide in MGMT-unmethylated GBM
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)
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.
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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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