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New research to target advanced oesophagogastic cancer

An Addenbrooke’s doctor is leading a trial to find improved treatments for patients with advanced oesophagogastric (OG) cancer.

CUH Consultant in gastro-intestinal oncology, Dr Lizzy Smyth, is the principal investigator for the ELEVATE study led by the Cancer Research UK’s Southampton Clinical Trials Unit.

Dr Lizzie Smyth head and shoulders
Dr Lizzie Smyth

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 drug 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 has also been used to treat certain types of OG cancers that have not responded to previous treatment.

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.

Around a third of people with OG cancer have low levels of a protein called MGMT, which helps to repair damaged DNA, and it is thought 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 increase the effectiveness of the immunotherapy treatment.

Dr Smyth 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.

Dr Lizzie Smyth, principal investigator

A total of 18 patients will be recruited to the ELEVATE trial. If the study is successful it could pave the way to a larger trial.

Kelly Cozens, senior trial manager for ELEVATE at the CRUK Southampton Clinical Trials Unit, said:

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.

Kelly Cozens, senior trial manager

The trial will also involve scientists at the Fitzgerald laboratory at the CRUK Cambridge Centre who will analyse tumour biopsies and blood samples from trial patients.

ELEVATE is being funded by Bristol Myers Squibb7 who make nivolumab.