King’s College London shared in September 2024 that an mRNA cancer immunotherapy (mRNA-4359), targeted for patients with lung cancer, melanoma, and other solid tumours, has shown promise in a Phase I trial. The first-in-human study of the therapy involved 19 patients with advanced stage cancers and found that the immunotherapy prompted an immune response against cancer and was well tolerated. Although this was a small study, the researchers are encouraged that their results support further investigations.
Potential in trial
The Phase I trial was designed to test the safety and tolerability of the immunotherapy, with secondary and tertiary objectives exploring the radiographic and immunological responses. 8 out of 16 patients whose responses could be evaluated demonstrated that tumour size did not increase, and no new tumours appeared.
The immunotherapy also activated the immune system in patients, generating immune cells that could recognise two proteins of interest: PD-L1 and IDO1. In some patients the immunotherapy increased levels of “important immune cells that can kill cancer cells” and reduced levels of other immune cells that inhibit the immune system’s response. The researchers acknowledge that their study was small and focussed on safety and finding an optimal dose. However, they continue to recruit patients with melanoma and lung cancer.
An important first step
UK Chief Investigator of the trial is Dr Debashis Sarker, Clinical Reader in Experimental Oncology in the School of Cancer and Pharmaceutical Sciences and consultant in medical oncology at Guy’s and St Thomas’ NHS Foundation Trust. Dr Sarker described the study as in “important first step in hopefully developing a new treatment for patients with advanced cancers”.
“We have shown that the therapy is well tolerated without serious side effects and can stimulate the body’s immune system in a way that could help to treat cancer more effectively. However, as this study has only involved a small number of patients to date, it’s too early to say how effective this could be for people with advanced stage cancer.”
The trial is continuing recruitment of patients in a “huge international effort” across the UK, USA, Spain, and Australia. Dr Kyle Holen, Senior Vice President and Head of Development, Therapeutics and Oncology, Moderna, is “encouraged” by the results. They demonstrate “potential to elicit strong antigen-specific T-cell responses while maintaining a manageable safety profile”.
“This novel approach could be a key component in shifting the tumour microenvironment towards a more immune-permissive state, offering potential hope for patients with advanced solid tumours.”
Professor Tariq Enver, Director of the Cancer Research UK City of London Centre, congratulated the team for “taking us a step closer to personalised cancer vaccines”.
“Through his role supporting training at our centre, Debashis continues to inspire the next generation of clinician scientists to drive life-saving breakthroughs in biological cancer therapies.”
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