The first human trial of a pioneering personalised cancer treatment will begin this week at Oxford University Hospitals NHS Trust, with the potential to tackle a wide range of late-stage cancers.
A major challenge in drug development is that all cancer patients respond differently to treatment, making it difficult to know how best to treat each patient. For the first time, a phase I trial in Oxford will investigate not only a new drug, called CXD101, but also a new test to predict which patients could be successfully treated by this class of drug.
'When patients' cancers do not respond to a treatment, this can cost tens of thousands of pounds and cause patients to suffer side effects for nothing,' said lead researcher Professor Nick La Thangue of Oxford University's Department of Oncology. 'Personalised medicine promises to prevent this by predicting how well a patient will respond to a drug before administering it and this is exactly what this trial will do. This is really the shape of things to come, and avoids the problem of testing drugs on patients who have little chance of benefiting from the treatment.'
The drug and associated test were first developed at Oxford University and are now being developed by spin-outs Celleron Therapeutics and Oxford Cancer Biomarkers, founded by Professors La Thangue and David Kerr and set up by the University's technology transfer company Isis Innovation.
The test measures levels of a protein called HR23B that could determine the effectiveness of CXD101 and similar drugs. The trial will involve 30-40 cancer patients, the first set of whom will be given increasing doses of CXD101 to determine the most effective dose. The second cohort of patients will then be tested for HR23B, and those with high levels of the protein will be treated with the best dose of CXD101.
CXD101 is a next-generation histone deacetylase (HDAC) inhibitor, a class of drug that kills cancer cells by blocking the vital functions of HDAC enzymes. HDAC enzymes are important for cell multiplication, migration and survival, so blocking them can stop tumours from growing and spreading, and even kill cancer cells entirely.
'HDAC inhibitors have had limited success in the past, but CXD101 works in a completely new way and has great potential to treat many different cancers,' said Professor La Thangue. 'Our previous research suggests that high levels of the HR23B protein make tumours more vulnerable to HDAC inhibitors, so we will now be putting this into practice to identify the patients who are most likely to benefit from CXD101. Any cancer could be high in HR23B, from breast cancers to blood cancers, so we are screening a broad range of patients to identify anyone who might benefit.'
The trial is a unique collaboration between Oxford University, Oxford University Hospitals NHS Trust, Celleron Therapeutics, Oxford Cancer Biomarkers and the ECMC (Experimental Cancer Medicine Centre) network. The Oxford ECMC, jointly funded by Cancer Research UK and the National Institute for Health Research, is led by Mark Middleton, Professor of Experimental Cancer Medicine at Oxford University's Department of Oncology, clinical lead for the CXD101 trial.
'This trial marks a lot of firsts – the first time the hospital has sponsored a trial of a new agent, the first time we will trial a predictive test along with a new drug, the first time CXD101 will be taken by patients, and even the development of the trial is new,' said Professor Middleton. 'We are working closely with the spin-outs to deliver the trial using a new model that allows the companies to set up the trial faster. This risk-sharing model encourages innovation, accelerates drug development and will bring benefits to UK plc in the long run.'
Conducting the majority of early-phase cancer clinical trials in the UK, Experimental Cancer Medicine Centres (ECMCs) provide infrastructure funding to enhance the quantity and quality of research in developing new medicines to help beat cancer. Each ECMC brings together lab-based experts in cancer biology with cancer doctors to speed up the flow of ideas from the lab bench to the patient’s bedside. Launched in 2007, the network of 18 ECMCs is jointly supported by Cancer Research UK, the National Institute for Health Research in England, and the Departments of Health of Scotland, Wales and Northern Ireland who, together, have provided £35m from 2007-2012 and a further £35m from 2012 to 2017. Find out more at www.ecmcnetwork.org.uk
Oxford Cancer Biomarkers translates ground-breaking scientific discovery into predictive biomarker diagnostic products that allow medicines to be personalised for the benefit of the cancer patient. Its unique platform, CancerNav®, isolates biomarkers which allow drugs to be tailored to the disease. It is a spin-out of the University of Oxford and is located on the Oxford Science Park. For more information, please visit www.oxfordcancerbiomarkers.com.
Celleron Therapeutics is a clinical stage cancer medicine company focussed on developing personalised therapies targeting epigenetic control. The company has built a proprietary platform around histone deacetylases and methyl-transferases. Celleron’s approach seeks to align the right drug with the right patient enabling a personalised approach to cancer therapy. The company is a spin-out from Oxford University and located on the Oxford Science Park. For more information see www.cellerontherapeutics.com
Oxford University’s Medical Sciences Division is one of the largest biomedical research centres in Europe, with over 2,500 people involved in research and more than 2,800 students. The University is rated the best in the world for medicine, and it is home to the UK’s top-ranked medical school.
From the genetic and molecular basis of disease to the latest advances in neuroscience, Oxford is at the forefront of medical research. It has one of the largest clinical trial portfolios in the UK and great expertise in taking discoveries from the lab into the clinic. Partnerships with the local NHS Trusts enable patients to benefit from close links between medical research and healthcare delivery.
A great strength of Oxford medicine is its long-standing network of clinical research units in Asia and Africa, enabling world-leading research on the most pressing global health challenges such as malaria, TB, HIV/AIDS and flu. Oxford is also renowned for its large-scale studies which examine the role of factors such as smoking, alcohol and diet on cancer, heart disease and other conditions.
Isis Innovation is the research and technology commercialisation company of the University of Oxford. We provide access to technology from Oxford researchers through intellectual property licensing, spin-out company formation and material sales, and to academic expertise through Oxford University Consulting.
Isis is the highest university patent filer in the UK and is ranked 1st in the UK for university spin-outs, having created more than 100 new companies in 25 years. In the last financial year we completed 395 licenses and consulting agreements with clients in 21 countries. The Isis Enterprise innovation management consultancy works with university, government and industrial clients from offices around the world. For updates on innovations from Oxford, follow Isis on LinkedIn and or subscribe at www.isis-innovation.com