CHICAGO — Results from a phase 1 clinical trial of the experimental cancer drug GRWD5769, which showed tumor shrinkage across six hard-to-treat cancer types when combined with immunotherapy, were presented at the American Society of Clinical Oncology’s annual meeting in Chicago. In the trial, 83 patients with cervical, bladder, liver, bowel, lung, or head and neck cancers received GRWD5769 alongside the immunotherapy cemiplimab.
GRWD5769 is an experimental tablet developed by Oxford-based Greywolf Therapeutics that works by inhibiting the enzyme ERAP1 (endoplasmic reticulum aminopeptidase 1), which cancer cells manipulate to hide from T-cells. All participants in the trial had previously failed to respond to treatment, and most had no remaining treatment options when they joined the study. Tumors shrank in 26 of the 83 patients, including 15 who experienced tumor reductions of at least 30%. The drug shrank tumors in all six cancer types included in the trial.
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 head and neck cancer patients, 51% of bowel cancer patients, and 55% of lung cancer patients. GRWD5769 tablets can be taken at home and were well tolerated by patients in the trial. The trial is ongoing, and a larger study is planned.
Prof Fiona Thistlethwaite, consultant medical oncologist and medical director of the Christie clinical research facility, was the principal investigator of the trial. “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.” Thistlethwaite said. She added, “What excites me about this trial is the combination of what we’re seeing – strong signals of efficacy across six tumour types that have shown great resistance to immunotherapy, with very few side-effects. That’s unusual at such an early stage, when we’re usually just looking at how safe it is. There’s a lot more work to be done before it reaches the clinic, but for a brand new drug to show that kind of profile so early – and in so many different types of hard-to-treat cancers – it gives me genuine optimism.”
Dr Samuel Godfrey, Cancer Research UK’s research information lead who was not involved in the trial, called the results encouraging but emphasized the need for further research. “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.”