Immunotherapy has transformed cancer treatment over the past decade, delivering significant improvements in outcomes for many patients. However, despite its success, a substantial proportion of cancers remain resistant to these therapies, limiting their impact across many tumour types.

New clinical trial data presented at the American Society of Clinical Oncology (ASCO) annual meeting has highlighted a promising approach that could help overcome one of immunotherapy’s biggest challenges: the ability of cancer cells to evade detection by the immune system.

Tackling Cancer’s Ability to Hide

Researchers have reported encouraging results from an early-stage clinical trial evaluating GRWD5769, an investigational therapy developed by UK biotechnology company Greywolf Therapeutics.

The oral treatment works by targeting ERAP1, an enzyme that plays a role in how tumour cells present antigens to the immune system. Many cancers exploit this biological pathway to avoid immune recognition, effectively concealing themselves from the body’s natural defences and reducing the effectiveness of immunotherapy.

By inhibiting ERAP1, GRWD5769 aims to expose previously hidden tumour markers, enabling the immune system to recognise and attack cancer cells more effectively.

The therapy was administered alongside cemiplimab, an established immunotherapy treatment, in patients whose cancers had progressed despite previous treatment.

Promising Results Across Six Cancer Types

The Phase I/II study involved 83 patients treated across multiple international cancer centres. Participants had advanced forms of six tumour types:

  • Bladder cancer
  • Cervical cancer
  • Colorectal cancer
  • Liver cancer
  • Non-small cell lung cancer
  • Head and neck cancer

Collectively, these cancers account for approximately one-third of all cancer diagnoses in the UK, highlighting the potential significance of a treatment approach that could be effective across multiple indications.

Researchers reported that 31% of patients experienced either tumour shrinkage or disease stabilisation, with some tumours shrinking by as much as 95%.

The greatest benefit was observed in patients with non-small cell lung cancer, where disease control lasting at least six months was achieved in up to 55% of participants.

Importantly, these results were observed in patients whose cancers had already stopped responding to standard treatment options, a setting where therapeutic choices are often limited.

A Growing Focus on Combination Immunotherapy

The findings reflect a broader trend within oncology research: developing combination approaches that enhance the effectiveness of existing immunotherapies.

Rather than directly targeting tumour cells, GRWD5769 is designed to improve immune recognition, helping immunotherapy treatments perform more effectively against cancers that have developed mechanisms to avoid detection.

This strategy represents an increasingly important area of research as scientists seek to address the significant proportion of patients who currently derive limited benefit from immune checkpoint inhibitors alone.

Professor Fiona Thistlewaite, Medical Director at The Christie, described the results as particularly encouraging given the breadth of activity observed across multiple tumour types and the favourable safety profile reported to date.

What Happens Next?

While the early results have generated considerable optimism, larger clinical trials will be needed to confirm efficacy, establish long-term outcomes and further evaluate safety.

Nevertheless, the study highlights the growing potential of therapies designed to modify antigen presentation and overcome immune escape mechanisms. If future trials replicate these findings, ERAP1 inhibition could emerge as an important new strategy for improving responses to immunotherapy across a range of difficult-to-treat cancers.

For the life sciences sector, the programme also serves as an example of how advances in tumour immunology continue to drive innovation, opening new opportunities for combination therapies that may extend the benefits of immunotherapy to a broader patient population.

What is Immunotherapy?

Immunotherapy is a form of cancer treatment that harnesses the body’s own immune system to recognise and destroy cancer cells.

Unlike traditional treatments such as chemotherapy, which directly target rapidly dividing cells, immunotherapies work by stimulating or enhancing immune responses against tumours.

Current immunotherapy approaches include:

  • Immune checkpoint inhibitors that remove biological “brakes” on immune cells
  • Monoclonal antibodies that target specific cancer-related proteins
  • Cellular therapies that engineer immune cells to attack cancer
  • Cancer vaccines designed to stimulate immune recognition

While immunotherapy has delivered significant advances in several cancer types, many tumours develop mechanisms to evade immune detection. Research programmes such as GRWD5769 are focused on overcoming these resistance mechanisms and expanding the number of patients who can benefit from immunotherapy-based treatment.

 

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