Break through immunotherapy drug trial at The Royal Marsden

The Royal Marsden is leading one of the world’s first immunotherapy trials for colorectal cancer that has been removed by surgery.

Immunotherapy has been a game-changer in the treatment of cancer, providing an option for cancers that are normally resistant to standard drugs, such as metastatic melanoma and kidney cancers. Researchers are now applying these findings to other cancer types, including colorectal cancer.

The study will recruit 402 patients from across the UK to explore whether adding a new drug (Avelumab) to standard chemotherapy reduces the risk of stage III bowel cancer coming back. 

Bowel cancer is the third most common type of cancer in the UK and one of the hardest to treat. New treatment strategies are therefore urgently needed. Most people with stage III bowel cancer – bowel cancer that has spread to local lymph glands – are currently treated with surgery and then chemotherapy. In some patients, unfortunately the cancer does come back. 

Avelumab is a checkpoint inhibitor immunotherapy, meaning it blocks proteins that stop the immune system from attacking cancer cells. So far it has only been licensed in the US for Merkel Cell Carcinoma and bladder cancer. Only people diagnosed with cancers that show ‘defective mismatch repair’ (dMMR) or ‘POLE exonuclease domain mutant’ bowel cancer can participate in the study.

NICE recommends that all patients with colorectal cancer are routinely tested for dMMR. Around one in 10 patients with operable stage III bowel cancer have tumours that are dMMR and around two in 100 patients have tumours with POLE mutations.  Patients with dMMR advanced, inoperable colorectal cancer (around four per cent of patients) have responded extremely well to immune checkpoint inhibitor drugs in clinical trials to date. These groups of people have lots of mutations in the genes of their tumours, which makes them more visible to the immune system and therefore more likely to respond to immunotherapy drugs. 

In the new trial, half of the patients will be treated with standard chemotherapy for 12 or 24 weeks while the other half will be treated with standard chemotherapy (12 or 24 weeks), followed by a further 24 weeks of Avelumab. Regular assessments will then take place over the next five years to measure response to treatment. 

This study will help researchers develop better treatments for patients, and will examine whether giving immunotherapy after chemotherapy can increase cure. 

This trial is supported by Merck and the NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research, London. The study is a collaboration with Royal Surrey County Hospital and the University of Oxford (Dr Tony Dhillon from Royal Surrey County Hospital NHS Foundation Trust is Chief Investigator of the study).