Date: 2014-05-08
Type of information:
phase: 1
Announcement: approval of the resumption of recruitment of new patients
Company: e-Therapeutics (UK)
Product: ETS2101 (dexanabinol)
Action
mechanism: ETS2101 (dexanabinol) is a synthetic cannabinoid previously studied in trauma patients. Its anti-cancer potential was identified by e-Therapeutics’ network pharmacology platform. This revealed the drug’s potential to overcome cancer cells’ ability to evade apoptosis – the suicide mechanism that is normally triggered if cells become dysfunctional – through impact on the network of proteins controlling the process. Preclinical work has provided empirical evidence that the drug induces apoptosis in cancer cells and has demonstrated broad activity against cancer cell lines. Findings of particular interest in experiments with brain cancer lines led the Company to support early evaluation of the drug in this setting in parallel with this broader phase I cancer study.
Disease: primary or secondary brain cancer
various solid tumors
Therapeutic area: Cancer - Oncology
Country: UK - USA
Trial
details: The brain cancer study is taking place at the UC San Diego Moores Cancer Center in La Jolla, California. Two UK centres, St James’s University Hospital in Leeds and the Northern Centre for Cancer Care at the Freeman Hospital in Newcastle, are conducting the solid tumor trial. Target enrolment is 24 patients in the brain cancer study and 45 patients in the solid tumor trial. 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”.
Latest
news: * On May 8, 2014, e-Therapeutics announced that the FDA has approved the resumption of recruitment of new patients into the Company’s investigator-led Phase Ia study of ETS2101 in brain cancer, conducted at the University of California San Diego Moores Cancer Centre. Recruitment was temporarily paused due to a drug storage issue which has been resolved to the satisfaction of the FDA, allowing the trial to continue to higher doses in further cohorts of patients. Patients who had received treatment with ETS2101 at the time of the temporary halt in recruitment were able to continue to be dosed in accordance with trial protocols. * On January 24, 2014, e-Therapeutics has announces that recruitment of patients into both of the ongoing phase I trials of ETS2101 has been halted temporarily because of a practical issue with stored drug for the trials. Patients already receiving treatment with ETS2101 will continue to be dosed in accordance with trial protocols. Relevant regulators are being notified and the Company is taking steps to enable recruitment to resume as soon as possible. Two phase I studies of ETS2101 are ongoing: an investigator-led study in brain cancer at the UC San Diego Moores Cancer Center in La Jolla, California and a study at three UK centres that is enrolling patients with a variety of solid tumours. A report of data from the UK study had been expected in Q1 2014; this may be delayed by the temporary halt in recruitment. * On January 7, 2014, e-Therapeutics has announced that the 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. * On December 18, 2012, e-Therapeutics has provided an update on the clinical trials of its cancer drug ETS2101. Two phase I studies, one in patients with primary or secondary brain cancer and the other in patients with various solid tumors, remain on track to report final data in Q4 2013 and Q1 2014, respectively. Interim data from the trials are expected in H1 2013. The phase I studies are designed to select appropriate doses for further trials, assess the safety and pharmacokinetics of ETS2101 and record any initial signs of anti-cancer activity. They have a dose-escalating design in which successive cohorts of patients receive higher doses of drug until a maximum tolerated dose is identified. To date 12 patients – two cohorts of three patients in each trial – have been treated. Some patients have completed multiple cycles of treatment with ETS2101; a number continue to be treated having received up to 11 weekly doses. No patient in either study has so far experienced dose-limiting toxicities or other serious drug-related adverse effects. Further dose escalation is therefore planned. * On March 29, 2012, e-Therapeutics has announced that regulatory agencies in the UK and the US have approved plans for phase I trials of the Company’s anti-cancer drug ETS2101 and that enrolment of patients into trials in these two countries will begin shortly.
