Interim data from the Phase I dose escalation part of the mRNA cancer immunotherapy (mRNA-4359), show promise in patients with advanced solid cancers.
The investigational mRNA cancer immunotherapy is targeted for 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 have found the immunotherapy created an immune response against cancer and was well tolerated, with adverse events including fatigue, injection site pain and fever.
Results from the Phase I trial, also the first-in-human study of the therapy, are being presented on Saturday, 14th September at the European Society of Medical Oncology conference in Barcelona by the UK Chief Investigator of the trial from King's College London and Guy's and St Thomas' NHS Foundation Trust. The trial is sponsored by Moderna.
The mRNA immunotherapy is just one of many cancer vaccines entering clinical trials around the world. The therapy works by presenting common markers of tumors to patients' immune systems, training them to recognize and fight cancer cells that express them and potentially eliminate cells that could suppress the immune system.
The Phase I trial was designed to test the safety and tolerability of the immunotherapy, and secondary and tertiary objectives were to assess the radiographic and immunological responses.
Eight out of sixteen patients who could have their responses evaluated were able to demonstrate their tumor size did not grow and no new tumors appeared.
Data also showed the 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). Researchers were able to show in some patients that the immunotherapy can increase levels of important immune cells that can kill cancer cells as well as reduced levels of other immune cells that can prevent the immune system from fighting cancer.
The results should be treated with caution, say the study authors, as the sample size was small and the primary objective of the study was to test for safety and determine the optimal dose of the immunotherapy. However, these promising early 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 more information on the safety and efficacy of the therapy.
The UK's Chief Investigator of the trial Dr Debashis Sarker, a Clinical Reader in Experimental Oncology at King's College London and a 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 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 continues to recruit patients with melanoma and lung cancers and is a huge international effort across the UK, USA, Spain and Australia."
We are encouraged by the Phase 1 results of mRNA-4359, which demonstrate its 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 tumor microenvironment toward a more immune-permissive state, offering potential hope for patients with advanced solid tumors."
Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology
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