New Drug Shows Promise in Shrinking Tumors

A new treatment aimed at preventing cancer cells from “hiding” from therapies has demonstrated the ability to reduce tumors by at least 30% in several common cancer types, according to initial trial results.

While immunotherapy has significantly boosted survival rates for many patients, it often struggles when tumor cells evade detection, allowing them to grow and spread. Researchers at Oxford have developed a drug intended to unmask these hidden cancer cells, enhancing the effectiveness of immunotherapy.

In a study conducted across the UK, France, Spain, and Australia, 83 patients with various cancers—including cervical, bladder, liver, bowel, lung, and head and neck—were administered the experimental drug, GRWD5769, in conjunction with immunotherapy using cemiplimab.

The research team, under the Christie NHS foundation trust in Manchester, found that tumors shrank in 26 participants, with 15 experiencing reductions of 30% or more. Notably, all participants had previously unsuccessful treatments and many were out of options when they entered the study. In fact, immunotherapy had either not worked or ceased to be effective.

This new smart drug was able to strip away the “invisibility cloaks” that tumors use to evade the immune response, thus allowing the cemiplimab treatment to effectively target and destroy cancerous cells.

These findings were shared at the American Society of Clinical Oncology’s annual meeting in Chicago, a significant event in the cancer research community.

GRWD5769 was found to be effective in all six cancer types included in the trial. The drug managed to halt disease progression for at least six months in 18% of cervical cancer cases, 32% for liver cancer, 36% for bladder cancer, 38% for head and neck cancer, and over half the patients with bowel (51%) and lung (55%) cancers.

Professor Fiona Thistlethwaite, the principal investigator and a medical director at the Christie clinical research facility, presented these early results. She noted that, “For a drug taken in tablet form, this is quite impressive. It’s still early, and more studies are necessary, but this drug, with its unique mechanism, clearly aids immunotherapy in working more effectively.”

The tablets, which can be conveniently taken at home, were developed by Greywolf Therapeutics, based in Oxford, and were generally well-tolerated by patients. The trial is ongoing, with plans for further studies on a larger scale.

Immunotherapy relies on T-cells—immune system cells that target infections and diseases—to find and eliminate cancer. Despite its transformative impact on cancer treatment, it is ineffective for about two-thirds of patients, primarily because tumors can evade detection.

Cancer cells manipulate an enzyme called ERAP1 (endoplasmic reticulum aminopeptidase 1) to obscure themselves from T-cells. GRWD5769 addresses this issue by inhibiting ERAP1, allowing T-cells to recognize previously hidden tumor cells.

Thistlethwaite remarked, “Immunotherapy has changed cancer treatment, yet the pool of patients benefiting remains relatively small. What excites me about this trial is the strong evidence of efficacy across these six difficult-to-treat cancers, with minimal side effects, which is unusual at this early stage when safety is usually the primary focus.”

Professor Stefan Symeonides, the trial’s UK lead investigator from the Edinburgh Cancer Centre and a professor at the University of Edinburgh, described the early results as “exciting,” emphasizing the significance of translating this novel approach into clinical trials for the benefit of patients.

Dr. Samuel Godfrey, Cancer Research UK’s research information lead who wasn’t involved in the trial, said, “Immunotherapy has revolutionized treatment for certain cancers but doesn’t work for everyone. This trial suggests how this new drug could enhance the effectiveness of immunotherapy, especially in cases where it previously failed. It’s indeed rare to see such results in patients whose cancers had stopped responding, particularly across various challenging cancer types, so these results are promising. However, this is still in the early stages, and larger trials will be essential to ascertain whether this method offers lasting benefits for patients.”