Cancer Research UK announces dosing of first patient in first-in-human trial with UCB4594 therapy

  • 28 October 2024

Summary

  • Cancer Research UK has announced a new Phase 1 clinical trial for people with advanced cancers associated with high HLA-G levels
  • The first patient received UCB4594 therapy at The Christie NHS Foundation Trust in Manchester
  • UCB4594 is a monoclonal antibody with effector functions and the potential to address significant unmet need in the treatment of a wide range of solid tumours
  • The clinical development of UCB4594 is part of a collaboration with UCB

Cancer Research UK are pleased to announce that the first patient has received treatment in a clinical trial for people with advanced cancers.

The UCB4594 study is designed to evaluate a newly developed immunotherapy, a type of drug that helps people’s bodies to recognise and fight cancer cells.

The drug, a monoclonal antibody called UCB4594, was developed by Brussels headquartered biopharmaceutical company UCB.

The first site for the study has opened at the National Institute for Health and Care Research (NIHR) Manchester Clinical Research Facility (CRF) at The Christie NHS Foundation Trust (The Christie) in Manchester. Further sites across the UK are planned as the trial progresses. 

Cancer therapies designed to use immune system processes, such as checkpoint inhibitors, have revolutionised cancer treatment. However, limitations are associated with checkpoint inhibitors* and there remains a pressing need for new and better immunotherapies to benefit a broader range of patients.

UCB4594 works by targeting human leukocyte antigen G (HLA-G). HLA-G molecules are usually found on the surface of cells forming the placenta. The antigens interact with the immune system and influence the immune system’s ability to accept and support the growth of a foetus (a process called “maternal-foetal tolerance”).** 

As a foetus is genetically different from the mother, it would normally be treated as a foreign invader by the immune system, and maternal-foetal tolerance processes activate to counteract the normal immune response. 

Certain types of cancer cells often take advantage of these processes by displaying HLA-G molecules on their surface to avoid being detected by the immune system. This can lead to poor outcomes for patients. 

Interfering with this process in non-pregnant patients is a potential way to prime the immune system to attack specific types of cancer cells with high levels of HLA-G molecules present.**  

The first part of the study has opened which is designed to assess which dose of UCB4594 treatment is most tolerable to participants. Positive results from the trial could lead to further studies into the effectiveness of UCB4594 in treating different types of cancer associated with high HLA-G levels.

Honorary Professor at The University of Manchester, Medical Oncology Consultant and Medical Director for the NIHR Manchester CRF at The Christie, Professor Fiona Thistlethwaite, who is leading the trial, said: 

“Despite many breakthroughs in cancer research, some cancers are still very challenging to treat, and patients deserve better treatment options. Targeting immune processes involving HLA-G could show promise as an approach for beating certain cancers. We look forward to seeing how this trial progresses to investigate whether UCB4594 is a tolerated and effective treatment for potentially treating patients with advanced cancers.”

Director of Cancer Research UK’s Centre for Drug Development, Dr Lars Erwig, said: 

“We are grateful to our industry partners who license the use of their cutting-edge therapies. It enables Cancer Research UK’s Centre for Drug Development to sponsor and manage more trials, potentially bringing new treatments, like UCB4594, to patients sooner. We thank current and future participants involved in this early-stage clinical trial, and we look forward to seeing how the study progresses.”

The clinical development of UCB4594 is part of a multi-year, multi-project and multi-agent collaboration with UCB, a global biopharmaceutical company,and Cancer Research UK’s Centre for Drug Development. Under the collaboration, Cancer Research UK are exclusively responsible for the design, sponsorship and delivery of the trial, while UCB will manufacture and provide UCB4594 for the trial. UCB retains exclusive rights to further develop and commercialise UCB4594 and will receive a licence to the results of the clinical trials from Cancer Research UK in return for undisclosed success-based milestone and royalty payments.

ENDS  

Professor Fiona Thistlethwaite, Dr Lars Erwig and other Cancer Research UK spokespeople are available for interview. For media enquiries, contact Fiona Scott in the Cancer Research UK press office on 020 3469 5128 or, out of hours, on 020 3469 8301.  

Notes to editor

*Dobosz et al. Challenges of the Immunotherapy: Perspectives and Limitations of the Immune Checkpoint Inhibitor Treatment; Int J Mol Sci. 2022 Mar; 23(5): 2847

**Wang et al. Harnessing the potential of HLA-G in cancer therapy: advances, challenges, and prospects. J Transl Med 22, 130 (2024).

About Cancer Research UK

  • Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research, influence and information.  
  • Cancer Research UK’s pioneering work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.   
  • Cancer Research UK has been at the heart of the progress that has already seen survival in the UK double in the last 40 years.   
  • Today, 2 in 4 people survive their cancer for at least 10 years. Cancer Research UK wants to accelerate progress and see 3 in 4 people surviving their cancer by 2034.  
  • Cancer Research UK supports research into the prevention and treatment of cancer through the work of over 4,000 scientists, doctors and nurses.  
  • Together with its partners and supporters, Cancer Research UK is working towards a world where people can live longer, better lives, free from the fear of cancer.  

For further information about Cancer Research UK's work or to find out how to support the charity, please call 0300 123 1022 or visit www.cancerresearchuk.org. Follow us on Twitter and Facebook.

About Cancer Research UK's Centre for Drug Development

Cancer Research UK has an impressive record of developing novel treatments for cancer. The Cancer Research UK Centre for Drug Development has been pioneering the development of new cancer treatments for 30 years, taking over 160 potential new anti-cancer agents into clinical trials in patients. Six of these new agents have made it to market, including temozolomide for brain cancer, abiraterone for prostate cancer and rucaparib for ovarian cancer. Two other drugs are in late development Phase 3 trials. Thirteen agents remain in active development with the potential to reach the market. It currently has a portfolio of 16 projects in preclinical development, Phase 1 or early Phase 2 clinical trials. www.cruk.org.uk/cdd  

About the Christie NHS Foundation Trust

  • The Christie is a specialist cancer centre in Manchester and has more than 120 years of expertise in cancer care, research and education. It is one of Europe’s leading cancer centres, treating over 60,000 patients a year. 
  • It is the largest provider of radiotherapy in the NHS (including high energy proton beam therapy and MR guided radiotherapy); it is home to the largest chemotherapy unit in the UK; and is a specialist surgical centre concentrating on rare cancers and complex procedures.
  • The Christie is one of Europe's largest experimental cancer medicine centres and an international leader in research and development with around 900 clinical studies ongoing at any one time. 
  • The Christie charity provides enhanced services for patients over and above what the NHS funds. 

Visit www.christie.nhs.uk to find out more or follow The Christie on social media @TheChristieNHS.

About the National Institute for Health and Care Research

The mission of the National Institute for Health and Care Research (NIHR) is to improve the health and wealth of the nation through research. We do this by:

  • Funding high quality, timely research that benefits the NHS, public health and social care;
  • Investing in world-class expertise, facilities and a skilled delivery workforce to translate discoveries into improved treatments and services;
  • Partnering with patients, service users, carers and communities, improving the relevance, quality and impact of our research;
  • Attracting, training and supporting the best researchers to tackle complex health and social care challenges;
  • Collaborating with other public funders, charities and industry to help shape a cohesive and globally competitive research system;
  • Funding applied global health research and training to meet the needs of the poorest people in low and middle income countries.

NIHR is funded by the Department of Health and Social Care. Its work in low and middle income countries is principally funded through UK international development funding from the UK government.

About The University of Manchester

The University of Manchester is recognised globally for its pioneering research, outstanding teaching and learning, and commitment to social responsibility. The Russell Group institution is ranked the 6th best university in the UK and 38th in the world (Academic Ranking of World Universities).

A truly international university, its community includes more than 44,000 students, 12,000 staff, and 500,000 alumni from 190 countries. Together, they are tackling the world’s biggest challenges – the University’s social and environmental impact is ranked in the top ten globally (Times Higher Education Impact Rankings).

The University is a powerhouse of research and discovery; 25 Nobel laureates are among its former staff and students; and it was ranked fifth for research power – the quality and scale of research and impact – in the UK government’s Research Excellence Framework (REF) 2021.

The institution is the most popular in the UK for undergraduate applications (UCAS 2021 cycle), and it is the it is the most targeted university by the UK’s leading employers (The Graduate Market, 2023).