Immune boosting antibody trialled in patients with oesophageal cancer

A new trial will look at whether an immunotherapy drug, given in combination with a type of chemotherapy, could be an effective treatment for patients with advanced oesophageal cancer.

The ELEVATE study is being led by the CRUK Southampton Clinical Trials Unit, based within the Centre for Cancer Immunology at the University of Southampton, alongside the Chief Investigator Dr Lizzy Smyth at Oxford University Hospitals NHS Foundation Trust.

Patients who have advanced oesophagogastric (OG) cancer that cannot be removed by surgery and has stopped responding to other treatments, will be given the immunotherapy drug nivolumab, alongside the chemotherapy temozolomide.

Nivolumab is a monoclonal antibody treatment that helps to boost the body’s own immune system by activating cells called T cells, helping them to find and destroy cancer cells. It is already used to treat some other cancers, such as melanoma, lung cancer, and head and neck cancers.

Nivolumab has also been used to treat certain types of OG cancers which have not responded to previous treatment, however only around 1 in 8 of these patients will see a response5. Researchers know that immunotherapy treatments, such as nivolumab, work better in patients who have lots of mutations in the DNA of their cancer cells and believe increasing the number of mutations might increase the chances of response to nivolumab.

Around a third of people with OG cancer have low levels of a protein called MGMT, which helps to repair damaged DNA, and it’s thought a chemotherapy drug called temozolomide may lead to more mutations to occur in the cancer cells of these patients.

Researchers hope that by treating patients with temozolomide before giving them nivolumab they can therefore increase the effectiveness of the immunotherapy treatment.

Dr Lizzy Smyth, consultant in gastro-intestinal oncology at Oxford University Hospitals NHS Foundation Trust and Chief Investigator of the ELEVATE trial, said: “Immunotherapy treatments can be beneficial in oesophageal cancers, but do not work in everyone, meaning some patients are left with very few treatment options. We are excited by the possibility of increasing the number of patients who can be helped by immunotherapy and hope this trial will show a benefit in combining temozolomide with nivolumab to increase the effectiveness of the treatment.”

A total of 18 patients will be recruited to the ELEVATE trial from 6-8 UK centres, with Cambridge University Hospitals NHS Foundation Trust opening the first site to recruitment.

If the study is successful it could pave the way to a larger trial to develop the treatment regime further and test nivolumab a larger cohort of patients.

Kelly Cozens, Senior Trial Manager for ELEVATE at the CRUK Southampton Clinical Trials Unit, said: “Improving outcomes for oesophageal cancer patients by finding effective new treatments is a priority area for the Southampton Clinical Trials Unit and we have vast experience in designing and running trials of immunotherapy treatments, and trials for OG patients. We hope that the ELEVATE trial can help increase our understanding of how we can make immunotherapy a viable option for more OG patients in the future.”

The trial will also involve scientists in Cambridge who will carry out the translational elements of the study. This will involve analysing tumour biopsies and blood samples from patients on the trial to examine the number of mutations and look for changes in the DNA and RNA of the cancer cells. These further tests will help researchers to understand more about the potential benefits of using nivolumab in combination with temozolomide.

ELEVATE is being funded by Bristol Myers Squibb who make nivolumab.