Immunotherapy treatment discovered that can have long-term survival benefit for Uveal melanoma

At CTRT, we are dedicated to finding better ways of treating cancer, as well as detecting, monitoring and understanding how cancer develops, particularly in rare cancers that don’t receive research funding elsewhere.

One of our trustees, Professor Paul Nathan has led a clinical trial at the Mount Vernon Cancer Centre, and has discovered a more successful way of treating Uveal melanoma.

Professor Paul Nathan

Uveal melanoma is a rare, but often high risk, type of cancer of the eye that frequently spreads to other parts of the body (particularly the liver). Unlike skin melanoma, once the cancer has spread, it does not respond very well to so-called immune checkpoint inhibitors, a type of cancer treatment that uses the body’s own immune system to recognize and fight off cancer cells. However, data from the clinical trial led by Professor Paul Nathan at the Mount Vernon Cancer Centre indicated that another type of immunotherapy can have long-term survival benefit in patients with metastatic uveal melanoma, a form of the disease that has spread.

The immunotherapy used in the trial, tebentafusp, works by bringing cells of the immune system close to the melanoma cells, effectively directing the immune cells to kill the cancer cells. Tebentafusp can perform this bridging role because it was designed as a ‘bispecific fusion protein’, which means that it latches on to pieces of a particular protein that melanoma cells have in abundance on their surface, as well as to a protein called CD3, that is present on T cells, a type of immune cell that is particularly efficient at killing cancer cells.

Initial reports showed that, at 1 year, tebentafusp improved the survival of patients with metastatic uveal melanoma, and the latest trial results which have been published recently in the New England Journal of Medicine, showed that the benefit is still seen at 3 years.

Nearly 400 patients, all of whom had previously untreated metastatic uveal melanoma, took part in the trial. They were randomly assigned to receive either tebentafusp or another treatment — a checkpoint inhibitor (pembrolizumab or ipilimumab) or chemotherapy (dacarbazine). At 3 years, more of the patients who had been given tebentafusp were still alive (27%) compared with the patients receiving any of the other treatments (18%). The side effects of tebentafusp were similar to those seen previously which included a rash, fever/chills, itching and low blood pressure. Very few patients receiving any of the drugs had to stop treatment, and there were no treatment-related deaths during the trial.

Tebentafusp clearly presents an advantage over current treatments for Uveal melanoma but unfortunately, it does not offer a cure at present. Moreover, tebentafusp only works in a subset of patients — making broadening tebentafusp’s potential benefit another priority.

Nevertheless, the future for tebentafusp, perhaps in combination with other treatments, looks very promising. Professor Nathan is leading an international trial due to begin in summer 2024 that will look at whether tebentafusp, if given after the primary treatment to tackle the melanoma in the eye, can reduce the number of patients who relapse with metastatic disease. This clinical trial will take place at many centres throughout Europe and North America and is being run by the European Organisation for Research and Treatment of Cancer.

The trial was run and funded by Immunocore, with some staffing costs at Mount Vernon Hospital supported by CTRT.

The Cancer Treatment and Research Trust continues to support Professor Nathan’s research thanks to your generosity. You can donate towards our melanoma research here

Research paper published in the New England Journal December 2023: Hassel, J.C. Three-year overall survival with tebentafusp in metastatic uveal melanoma. N Engl J Med. 2023 Dec 14;389(24):2256-2266. doi: 10.1056/NEJMoa2304753.