Modified version of herpes simplex virus shows promise against range of advanced cancers in early trial results
A quarter of patients on the clinical trial showed signs of responding to the "genetically engineered, cancer-killing virus".
Researchers have found that RP2 – a modified version of the herpes simplex virus – showed signs of effectiveness, on its own or in combination with the immunotherapy nivolumab, in a quarter of patients with a range of advanced cancers.
Patients on the phase I trial had cancers including skin, oesophageal and head and neck cancer and had exhausted other treatments, including by failing to respond to checkpoint inhibitor immunotherapy.
A team at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research, London, assessed the cancer-killing virus on its own in nine patients and in combination with nivolumab in an initial 30 patients in the ongoing phase I trial.
The early stage study, sponsored by the drug’s manufacturer Replimune, is testing the safety and dosage of RP2, as well as evaluating its ability to shrink tumours.
The genetically engineered RP2 virus, which is injected directly into the tumours, is designed to have a dual action against tumours. It multiplies inside cancer cells to burst them from within, and it also blocks a protein known as CTLA-4 – releasing the brakes on the immune system and increasing its ability to kill cancer cells.
Three out of nine patients treated with RP2 on its own benefitted from the treatment and saw their tumours shrink. One patient with salivary gland cancer saw their tumour disappear completely and remains free of cancer 15 months after starting treatment.
All patients involved in the trial had very advanced cancers which had failed to respond to, or were not eligible for, standard care options.
Krzysztof Wojkowski, 39, a builder from West London, was diagnosed with Mucoepidermoid carcinoma, a type of salivary gland cancer, in May 2017. After multiple surgeries, he was told that there were no treatment options left, before being given the opportunity to join the RP2 trial at The Royal Marsden in 2020.
He said: “I was told there were no options left for me and I was receiving end of life care, it was devastating, so it was incredible to be given the chance to join the trial at The Royal Marsden, it was my final lifeline. I had injections every two weeks for five weeks which completely eradicated my cancer. I’ve been cancer free for two years now, it’s a true miracle, there is no other word to describe it. I’ve been able to work as a builder again and spend time with my family, there’s nothing I can’t do.”
Researchers looked at patient biopsies before and after RP2 injections and found positive changes in the tumour’s ‘immune microenvironment’: the area immediately around the tumour. Injections led to more immune cells in the area, including CD8+ T-cells, and ‘switched on’ genes linked to the ‘anti-cancer’ immune response.
Researchers found that most side effects of RP2 were mild – some of the most common were fever, chills, and fatigue. None of the side effects were serious enough to require medical intervention.
Next, researchers hope to continue exploring the potential of RP2 in a larger number of patients.
Study leader Professor Kevin Harrington, Consultant Oncologist at The Royal Marsden NHS Foundation
Trust and Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, said:
“Our study shows that a genetically engineered, cancer-killing virus can deliver a one-two punch against tumours – directly destroying cancer cells from within while also calling in the immune system against them.
“It is rare to see such good response rates in early-stage clinical trials, as their primary aim is to test treatment safety and they involve patients with very advanced cancers for whom current treatments have stopped working.
“Our initial trial findings suggest that a genetically engineered form of the herpes virus could potentially become a new treatment option for some patients with advanced cancers – including those who haven’t responded to other forms of immunotherapy. I am keen to see if we continue to see benefits as we treat increased numbers of patients.”