DelMar Pharmaceuticals, Inc. has unveiled its third clinical trial site at the Brain Tumour Centre at University of California, San Francisco (UCSF). DelMar is currently conducting a phase I/II dose-escalation study designed to assess the safety and activity of VAL-083 as a potential treatment for brain cancer patients suffering from glioblastoma multiforme (GBM) who have failed standard therapies and have no viable treatment options.
Jeffrey Bacha, DelMar’s president & CEO said, “Opening UCSF as the first West Coast clinical site for our VAL-083 glioblastoma clinical trial is a key step in our strategy to increase patient access. This new site will also help accelerate the overall development of VAL-083 as a muchneeded, new therapy for refractory glioblastoma multiforme, the most common and aggressive form of brain cancer.”
The Brain Tumour Centre at UCSF is one of the largest and most comprehensive programmes for brain tumour treatment in the US, and it includes the Division of Neuro-oncology, the Brain Tumour Research Centre, and the Division of Translational Research. DelMar also has clinical trial sites at the Sarah Cannon Research Institute in Nashville, Tennessee and at a second centre in Sarasota, Florida.
In June this year, DelMar presented interim clinical data from the ongoing clinical trial at the American Society of Clinical Oncology (ASCO) annual meeting. Highlights of DelMar’s ASCO data include: VAL-083 therapy is well tolerated by patients at doses studied to date; while doses tested to date were well below those used in historical clinical studies, 25 per cent of GBM patients and 17 per cent of secondary-progressive brain cancer patients showed stable disease or tumour regression in response to VAL-083 treatment. These patients had failed prior therapy before being treated with VAL-083; maximum tolerated dose (MTD) has not yet been reached; continued dose escalation and accelerated development of VAL-083 in GBM is warranted; pharmacokinetic analysis shows dose-dependent increase in plasma exposure following doses of VAL-083, which suggests higher dosing is likely to result in stronger tumour response.
VAL-083 represents a ‘first-in-class’ small-molecule chemotherapeutic. VAL-083 has been assessed in multiple NCI-sponsored clinical studies in various cancers including lung, brain, cervical, ovarian tumours and leukaemia. Published pre-clinical and clinical data suggest that VAL-083 may be active against a range of tumour types. VAL-083 is approved as a cancer chemotherapeutic in China for the treatment of chronic myelogenous leukemia and lung cancer.
Based on published research, the mechanism of action of VAL-083 is understood to be a bifunctional alkylating agent; however, the functional groups associated with alkylating events has been shown to differ from other alkylating agents used in the treatment of GBM.
VAL-083 has previously demonstrated activity in cyclophosphamide, BCNU and phenylanine mustard resistant cell lines and no evidence of cross-resistance has been encountered in published clinical studies. Based on the presumed alkylating functionality of VAL-083, published literature suggests that DNA repair mechanisms associated with Temodar and nitrosourea resistance, such as 06-methylguanine methyltransferase (MGMT), may not confer resistance to VAL-083.
VAL-083 readily crosses the blood brain barrier where it maintains a long half-life in comparison to the plasma. Published preclinical and clinical research demonstrates that VAL-083 is selective for brain tumour tissue. VAL-083 has been assessed in multiple studies as chemotherapy in the treatment of newly diagnosed and recurrent brain tumours. In general, tumor regression was achieved following therapy in greater than 40 percent of patients treated and stabilization was achieved in an additional 20 to 30 per cent. In published clinical studies, VAL-083 has previously been shown to have a statistically significant impact on median survival in high-grade gliomas when combined with radiation versus radiation alone.
The main dose-limiting toxicity related to the administration of VAL-083 in previous clinical studies was myelosuppression. No significant hepatic, renal or pulmonary toxicity has been reported in the literature or overseas commercial experience.
The phase I/II study is an open-label, single arm dose-escalation study designed to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of VAL-083 in patients with histologically confirmed initial diagnosis of primary WHO Grade IV malignant glioma (GBM), now recurrent. Patients with prior low-grade glioma or anaplastic glioma are eligible, if histologic assessment demonstrates transformation to GBM. GBM patients must have been previously treated for GBM with surgery and/or radiation, if appropriate, and must have failed both Avastin and Temodar, unless either or both are contraindicated.
Del Mar Pharmaceuticals was founded to develop and commercialize proven cancer therapies in new orphan drug indications where patients are failing modern targeted or biologic treatments.