Interim data from a Phase I dose-escalation trial of mRNA cancer immunotherapy (mRNA-4359) are promising in patients with advanced solid cancers.
The investigational mRNA cancer immunotherapy is targeting patients with lung cancer, melanoma and other solid tumors. Nineteen patients with advanced-stage cancers received between one and nine doses of the immunotherapy treatment. Scientists found that the immunotherapy created an immune response against the cancer and was well tolerated, with adverse effects including fatigue, pain at the injection site and fever.
Results of the Phase I trial, also the first human study of the therapy, will be presented on Saturday 14th.He In September, at the European Society for Medical Oncology conference in Barcelona, the chief investigator of the trial from King’s College London and the UK’s Guy’s and St Thomas’ NHS Foundation Trust, sponsored by Moderna.
mRNA immunotherapy is just one of many cancer vaccines in clinical trials around the world. The therapy works by presenting common tumor markers to patients’ immune systems, training them to recognize and fight cancer cells that express them and potentially kill cells that might suppress the immune system.
The phase I trial was designed to test the safety and tolerability of immunotherapy, and the secondary and tertiary objectives were to evaluate radiographic and immunological responses.
Of the sixteen patients whose responses could be evaluated, eight were able to demonstrate that the size of their tumors did not increase and that no new tumors appeared.
The data also showed that mRNA immunotherapy could activate the immune system in many patients, generating immune cells in the blood that could recognize the two proteins of interest (PD-L1 and IDO1). The researchers were able to show in some patients that immunotherapy can increase the levels of important immune cells that can kill cancer cells, as well as reduce the levels of other immune cells that can prevent the immune system from fighting cancer.
The results should be taken with caution, the study authors say, as the sample size was small and the primary goal of the study was to test safety and determine the optimal dose of immunotherapy. However, these promising preliminary results support further research into mRNA-4359.
The trial continues to recruit patients with melanoma and lung cancer in combination with the immunotherapy drug pembrolizumab to provide further information on the safety and efficacy of the therapy.
The UK trial’s lead investigator, Dr Debashis Sarker, clinical professor of experimental oncology at King’s College London and consultant in medical oncology at Guy’s and St Thomas’ NHS Foundation Trust, said: “This study evaluating an mRNA cancer immunotherapy is an important first step towards hopefully developing a new treatment for patients with advanced cancers.
“We have shown that the therapy is well tolerated and does not cause serious side effects, and that it can boost the body’s immune system in a way that could help treat cancer more effectively. However, as this study has only involved a small number of patients to date, it is too early to say how effective it might be for people with advanced cancer.
“The trial continues to recruit patients with melanoma and lung cancer and is a huge international effort in the UK, US, Spain and Australia.”
Dr. Kyle Holen, Senior Vice President and Head of Development, Therapeutics and Oncology at Moderna, said, “We are encouraged by the Phase 1 results for mRNA-4359, which demonstrate its potential to generate strong antigen-specific T cell responses while maintaining a manageable safety profile.
“This novel approach could be a key component in shifting the tumor microenvironment toward a more immunologically permissive state, offering potential hope for patients with advanced solid tumors.”