A new smart drug that prevents cancer cells from hiding from the immune system has shown promising results in an early clinical trial, shrinking tumours by at least 30% in patients with six of the world's most common forms of cancer.
Immunotherapy treatments have improved survival rates for many cancer patients, but their effectiveness can stall or fail when tumour cells conceal themselves and spread. Researchers at the University of Oxford have developed a drug designed to stop this concealment, allowing immunotherapy to identify and destroy cancer cells.
In a trial conducted across the UK, France, Spain, and Australia, 83 patients with cervical, bladder, liver, bowel, lung, or head and neck cancers received the experimental drug, GRWD5769, alongside the immunotherapy treatment cemiplimab. The trial was led by the Christie NHS Foundation Trust in Manchester, England.
Results showed that tumours shrank in 26 patients, with 15 experiencing reductions of at least 30%. All participants had previously failed to respond to treatment, and most had no other options left. Crucially, immunotherapy had either not worked or had stopped working.
GRWD5769 works by removing the “invisibility cloaks” from tumour cells, exposing them to T-cells—immune system cells that attack infections and diseases. This allows cemiplimab to pinpoint and destroy the cancer.
The findings were presented at the American Society of Clinical Oncology’s annual meeting in Chicago, the world’s largest cancer conference. The drug halted disease progression for at least six months in 18% of cervical cancer patients, 32% of liver cancer patients, 36% of bladder cancer patients, 38% of those with head and neck cancer, and more than half of bowel (51%) and lung (55%) cancer patients.
Prof Fiona Thistlethwaite, principal investigator and consultant medical oncologist at the Christie, said: “For a drug that is given as a tablet, this is very impressive. It’s early days, and we need further studies, but this is a new drug with a new mechanism that clearly helps immunotherapy perform more effectively.”
The tablets, developed by Oxford-based Greywolf Therapeutics, can be taken at home and were well tolerated. The trial is ongoing, with a larger study planned.
Tumours evade the immune system by manipulating an enzyme called ERAP1 (endoplasmic reticulum aminopeptidase 1). By altering this enzyme, cancer cells hide from T-cells. GRWD5769 inhibits ERAP1, effectively removing the cancer’s invisibility cloak and making tumour cells visible to T-cells.
Prof Stefan Symeonides, UK principal investigator and consultant medical oncologist at the Edinburgh Cancer Centre, described the early results as “exciting.” He said: “It is fantastic to have been able to bring this promising new immunotherapy approach through to clinical trials and to see our patients benefiting.”
Dr Samuel Godfrey, research information lead at Cancer Research UK, who was not involved in the trial, commented: “Immunotherapy has transformed treatment for some cancers but it doesn’t yet work for everyone. This trial seems to show how this new drug could make immunotherapy more effective, including in some cases where immunotherapy had previously failed. It is unusual to see such outcomes in patients whose cancers have already stopped responding to treatment, particularly across several hard-to-treat cancer types, so these results are encouraging. However, this is still an early-stage study, and larger trials will be needed to determine whether this approach can deliver lasting benefits for patients.”
