MIDDLETON GROUP

EARLY PHASE, MELANOMA AND UPPER GASTROINTESTINAL CANCER TRIALS

Our aim is to bring the excellent science in Oxford to cancer patients. We develop new treatments or combinations of treatments designed to address specific vulnerabilities in patients’ tumours, working with academic and industry collaborators. To deliver this we have established the infrastructure to perform detailed analyses of tumours before, during and after intervention to select patients; to test our a priori hypotheses; and to better understand the biological effects of treatment.

We work on developing new cancer drugs and many of these are now part of standard care including MEK inhibitors, oncolytic viruses and checkpoint blockers. Another example is Tebentafusp, which we developed with the University spin out Immunocore. We helped the company design the early clinical programme and identified Tebentafusp’s activity in uveal melanoma. This led to definitive trials showing improved survival and to licensing.

Recently we have seen incredible advances in the treatment of advanced melanoma and cancers of the oesophagus, stomach, bile ducts and liver. The challenges now are to understand why not all patients benefit from the new drugs at our disposal. Tumour characteristics or signatures are being explored to identify patients who are likely to benefit from particular treatments and to make informed treatment decisions on the best combinations of drugs to use in the clinic.

We look to deliver smaller trials involving subsets of patients. These have the ability to change patient care, by focussing our efforts on tightly defined clinical populations to maximise differences in outcome, distinct from one-size-fits-all phase 3 trials with purely correlative translational studies. Through the Oncology Clinical Trials Office (OCTO; setting up studies to run in centres all around Europe) and the Oxford Cancer Trials (running trials in the Oxford Cancer and Haematology Centre) we have established one of the largest academic early phase trials portfolios in Europe.

USING LIQUID BIOPSIES TO DIAGNOSE CANCER EARLIER AND GUIDE TREATMENT

A second objective is to identify tools to help determine how best to treat patients. Currently our focus is on the application of ctDNA technologies to optimise the selection and timing of anti-cancer drug treatments, for example in the TebeMRD trial. We also work on diagnosing cancers earlier, assessing multi-cancer early detection tests in symptomatic patients, including in the >6000 patient SYMPLIFY study. This built on work piloting rapid diagnostic pathways for patients with vague symptoms (the SCAN pathway), which is now established as standard of care. We have more studies planned to test a wider range of diagnostics, such as ARMADILO, and to evaluate new treatments tailored for when cancers are detected early.

DIGITAL TRIALS

We have demonstrated the potential in our trials to accelerate cancer research by using registry data as a viable source of clinical trial data. This reduces resource burden whilst maintaining data validity in delivering large-scale studies. The MyMelanoma programme is an example of this, being open to NHS patients anywhere in the UK and now involving over 15,000 participants. Our aim is to bring research to patients where they live, rather than requiring them to come to hospitals, and to give them the choice over which aspects of the work they want to engage. The programme is being extended to other cancer types and to people with cancer pre-disposition.

GROUP INFORMATION

I run my trials in the Oxford Cancer Trials Unit at the Churchill Hospital, delivering the translational elements through research collaborators both in Oxford and around the world. Academic studies are developed with OCTO and the Primary Care Clinical Trials Unit, often in partnership with national and international consortia. As a clinical researcher I don’t run a single group and instead lead a series of teams focussed on particular trials or translational research questions.  This way of working, and my focus on trials that run over several years, means that I do not offer Masters and DPhil projects other than through my collaborators. These can be found on the ‘Study with us’ pages of the Department and of Oxford Cancer.