- Company confirms 40mg/square meter as the maximum tolerated dose (MTD) for advancement into registration-directed clinical trials -
- Preparation underway to initiate registration-directed Phase II/III clinical trials with VAL-083 in patients with GBM in 2016 -
VANCOUVER, British Columbia and MENLO PARK, Calif., Oct. 21, 2015 /PRNewswire/ -- DelMar Pharmaceuticals, Inc. (OTCQX: DMPI) ("DelMar" and the "Company"), a biopharmaceutical company focused on the development and commercialization of new cancer therapies, announced today that the 14-patient expansion cohort of its Phase II clinical study of VAL-083 (dianhydrogalactitol) in patients with refractory glioblastoma multiforme (GBM) is now fully enrolled.
"We are pleased to confirm that 14 patients have now received at least one course of treatment in the Phase II expansion of this study," stated Jeffrey Bacha, president & CEO of DelMar Pharmaceuticals. "The fact that we achieved full enrollment far more rapidly than projected, highlights the critical need for new therapies in the treatment of refractory GBM."
Patients enrolled in DelMar's clinical trial have failed both front-line therapy with temozolomide and second-line Avastin and, in most cases, one or more salvage therapies.
"Currently available treatments unfortunately fail to offer any meaningful recourse to slow tumor progression or to extend life in the majority of GBM patients," Mr. Bacha continued. "We believe VAL-083 offers promise as a modern solution to the tremendous unmet medical need for a new therapy for GBM patients who have failed – or are unlikely to respond to – currently available treatments."
Data from the Phase I dose-escalation portion of the multicenter Phase I/II clinical study with VAL-083 in patients with recurrent GBM were presented at ASCO 2015. Dose limiting toxicity was observed at a dose of 50mg/m2/day; no drug-related severe adverse events were reported and myelosuppression was mild at doses <40mg/m2/day.
The Company also provided an update at the GBM2015 scientific meeting on a sub-group analysis for patients receiving up to 5 mg/m2 daily x 3 every 21 days (low dose) versus those patients receiving 30mg/m2 or 40mg/m2 (therapeutic dose) of VAL-083 in the study. The sub-group analysis supports a dose-dependent and clinically meaningful survival benefit in GBM patients whose tumors had progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.
DelMar commenced enrollment in the 14-patient expansion cohort for the trial in GBM near the end of the second quarter of 2015 at the University of California, San Francisco, the Mayo Clinic in Rochester, MN and three sites affiliated with the Sarah Cannon Cancer Research Institute in Nashville, TN, Sarasota, FL and Denver, CO. The purpose of the expansion cohort is to gain additional information about the safety and efficacy of VAL-083 at a 40mg/m2 dose prior to advancement into registration-directed Phase II/III clinical trials.
To further explore the therapeutic window of VAL-083, DelMar also enrolled three (3) patients an interim dose of 45mg/m2.
"Based on the well-tolerated nature of treatment observed at the 40mg/m2 dose compared to the dose limiting toxicity observed at 50mg/m2, our clinical advisors suggested that exploration of an interim dose at 45mg/m2 was warranted," stated Dr. Dennis Brown, DelMar's Chief Scientific Officer. "Preliminary analysis of safety data from the 45mg/m2 cohort and from patients enrolled in the Phase II expansion cohort (at 40mg/m2) supports the 40mg/m2 dose as an appropriate dose for advancement into registration-directed clinical trials."
DelMar expects to provide ongoing updates of data during the Phase II trial at oncology and scientific meetings during the remainder of 2015 and into 2016.
Mr. Bacha concluded, "Given that we have now completed enrollment in the Phase II expansion phase of our current study, we remain on track to initiate Phase II/III registration-directed studies within the next nine to twelve months. The design and timing of initiation of the registration-directed clinical trial will depend on review of the data from this clinical study and discussions with the FDA and our clinical advisors."
Further information on the design of DelMar's trial with VAL-083 as a treatment for GBM may be found on the company's website at http://www.delmarpharma.com/clinical-trial.html.
About VAL-083
VAL-083 is a "first-in-class," small-molecule chemotherapeutic. In more than 40 Phase I and II clinical studies sponsored by the U.S. National Cancer Institute, VAL-083 demonstrated safety and efficacy in treating a number of cancers including lung, brain, cervical, ovarian tumors and leukemia both as a single-agent and in combination with other treatments. VAL-083 is approved in China for the treatment of chronic myelogenous leukemia (CML) and lung cancer, and has received orphan drug designation in Europe and the U.S. for the treatment of malignant gliomas.
DelMar has demonstrated that VAL-083's anti-tumor activity is unaffected by the expression of MGMT, a DNA repair enzyme that is implicated in chemotherapy resistance and poor outcomes in GBM patients following standard front-line treatment with Temodar® (temozolomide).
DelMar's Phase I/II clinical trial in refractory GBM is being conducted in accordance with a protocol that has been filed with the U.S. Food and Drug Administration (FDA). Patients have been enrolled at five clinical centers in the United States: Mayo Clinic (Rochester, MN); UCSF (San Francisco, CA) and three centers associated with the Sarah Cannon Cancer Research Institute (Nashville, TN, Sarasota, FL and Denver, CO).
In the Phase I dose-escalation portion of the study, VAL-083 was well tolerated at doses up to 40mg/m2 using a regimen of daily x 3 every 21 days. Adverse events were typically mild to moderate; no treatment-related serious adverse events reported at doses up to 40 mg/m2. Dose limiting toxicity (DLT) defined by thrombocytopenia (low platelet counts) was observed in two of six (33%) of patients at 50 mg/m2. Generally, DLT-related symptoms resolved rapidly and spontaneously without concomitant treatment, although one patient who presented with hemorrhoids received a platelet transfusion as a precautionary measure.
Sub-group analysis of data from the Phase I dose-escalation portion of the study suggests a dose-dependent and clinically meaningful survival benefit following treatment with VAL-083 in GBM patients whose tumors had progressed following standard treatment with temozolomide, radiotherapy, bevacizumab and a range of salvage therapies.
Patients in a low dose (<5mg/m2) sub-group had a median survival of approximately five (5) months versus median survival of approximately nine (9) months for patients in the therapeutic dose (30mg/m2 & 40mg/m2) sub-group following initiation of VAL-083 treatment. Increased survival was observed at 6, 9 and 12 months following initiation of treatment with VAL-083 in the therapeutic dose sub-group compared to the low dose sub-group.
Further details can be found at http://www.delmarpharma.com/scientific-publications.html.
About DelMar Pharmaceuticals, Inc.
DelMar Pharmaceuticals, Inc. was founded to develop and commercialize new cancer therapies in indications where patients are failing or have become intolerable to modern targeted or biologic treatments. The Company's lead drug in development, VAL-083, is currently undergoing clinical trials in the U.S. as a potential treatment for refractory glioblastoma multiforme. VAL-083 has been extensively studied by U.S. National Cancer Institute, and is currently approved for the treatment of chronic myelogenous leukemia and lung cancer in China. Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumor types via a novel mechanism of action that could provide improved treatment options for patients.
For further information, please visit http://delmarpharma.com/; or contact DelMar Pharmaceuticals Investor Relations: [email protected] / (604) 629-5989. Connect with the Company on Twitter, LinkedIn, Facebook, and Google+. Investor Relations Counsel: Amato & Partners LLC.
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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SOURCE DelMar Pharmaceuticals, Inc.
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