OXFORD & NEWCASTLE, England--(BUSINESS WIRE)--e-Therapeutics plc today announces that the investigator-led phase I trial of ETS2101 in brain cancer will continue into 2014. Five dose escalation steps have been completed without any drug-related serious adverse events and the investigator therefore intends to enrol further patients at higher dose levels.
The trial includes patients with advanced primary or secondary brain cancer that has recurred after treatment with established therapies. It is being conducted by Professor Santosh Kesari, MD, PhD, director of neuro-oncology at the UC San Diego Moores Cancer Center in La Jolla, California. The primary objective of the trial is to evaluate the safety of ETS2101 and establish an appropriate dose for further studies. Secondary objectives include initial assessment of the drug’s activity and study of its pharmacokinetics (distribution in the body and brain).
Under the protocol, groups of patients are treated at successively higher doses until a maximum tolerated dose is found. Fifteen patients have now completed treatment at doses up to 24 mg/kg body weight. At all doses tested so far, ETS2101 has been generally well tolerated. No objective tumour responses have been reported based on the Response Assessment in Neuro-Oncology (RANO) Working Group criteria (see notes). Detailed data on safety and other endpoints will be submitted to a medical meeting when treatment and follow up of all patients is completed.
Professor Kesari said: “With an absence of safety concerns to date, we plan to evaluate at least one further dose level of ETS2101. Preliminary pharmacokinetic data from the study and non-clinical data also support this plan.”
Stephen Self, Development Director at e-Therapeutics, added: “The brain cancer trial complements our UK phase I study in patients with various tumours and will help us decide on next steps with ETS2101. We appreciate the contribution of Professor Kesari and his patients to the investigation of the drug in an area of considerable unmet need and look forward to further findings from the trial.”
About the RANO criteria
The ETS2101 phase I trial in brain cancer uses the Response Assessment in Neuro-Oncology (RANO) Working Group criteria to assess anti-tumour effects. The criteria incorporate information from radiographic scans and neurological examinations and also take account of patients’ Karnofsky Performance Status and steroid use. If other measures are satisfied, tumour responses are classified as “complete” if there is total disappearance of lesions or “partial” if there is at least a 50% reduction in the size of all measurable lesions for at least 4 weeks; for some brain tumour types not including high-grade gliomas or brain metastases 25-50% reductions are classified as “minor responses”.
ETS2101 (dexanabinol) is a synthetic cannabinoid previously studied in trauma patients. Application of network pharmacology by e-Therapeutics suggested that the drug has potential in cancer. Preclinical studies then provided evidence of activity in a wide variety of cancer cell lines. Two phase I studies of ETS2101 are ongoing, one in patients with primary or secondary brain cancers and one in patients with various advanced solid tumours.
About brain cancers
According to the American Brain Tumor Association, around 24,000 patients were expected to be diagnosed with a primary malignant brain tumour during 2013 in the US alone. Some 80% of primary malignant brain tumours are gliomas, a broad term which includes all tumours arising from the supportive tissue of the brain. Secondary brain cancers arise when cancer in other tissues spreads (metastasises) to the brain: the incidence of secondary brain cancer is thought to be higher than that of primary brain cancer.
About UC San Diego Moores Cancer Center
UC San Diego Moores Cancer Center is home to nearly 350 medical and radiation oncologists, cancer surgeons, and researchers. It is one of only 41 National Cancer Institute-designated comprehensive cancer centres in the United States, a rare honour distinguishing exceptionally high achievement in research, clinical care, education and community outreach and partnerships. For more information, visit www.cancer.ucsd.edu. Specific information about Professor Santosh Kesari and his work can be found at www.kesarilab.ucsd.edu/Pages/default.aspx
e-Therapeutics is an AIM-listed biotechnology company with a proprietary platform in network pharmacology, an innovative new approach to drug discovery based on advances in network science and chemical biology. The Company’s discovery and development activity is focused in cancer and disorders of the nervous system. e-Therapeutics is based at sites in Oxford and Newcastle, UK. For more information about the Company please visit www.etherapeutics.co.uk.