Interim results from a Phase I dose-escalation study of mRNA-4359, an mRNA cancer immunotherapy developed by Moderna, suggest potential benefits for patients with advanced solid cancers. The first-in-human trial, presented at the European Society of Medical Oncology conference, evaluated the safety, tolerability, and preliminary efficacy of the immunotherapy in patients with lung cancer, melanoma, and other solid tumors.
The trial involved 19 patients with advanced-stage cancers who received between one and nine doses of mRNA-4359. The primary objective was to assess the safety and tolerability of the immunotherapy, while secondary and tertiary objectives included evaluating radiographic and immunological responses.
Early data indicated that the immunotherapy was generally well-tolerated, with adverse events including fatigue, injection site pain, and fever. Importantly, the treatment appeared to stimulate an immune response against cancer. Eight out of sixteen patients with evaluable responses demonstrated stable disease, meaning their tumor size did not increase, and no new tumors appeared.
Further analysis revealed that mRNA-4359 could activate the immune system in many patients, generating immune cells in the blood capable of recognizing PD-L1 and IDO1, two proteins of interest. In some patients, the immunotherapy increased levels of immune cells that can kill cancer cells and reduced levels of immune cells that can suppress the immune system.
Dr. Debashis Sarker, the UK Chief Investigator of the trial from King’s College London and Guy’s & St Thomas’ NHS Foundation Trust, noted, "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."
Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology, stated, "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."
Study Limitations and Future Directions
The study authors caution that the sample size was small, and the primary objective was to test for safety and determine the optimal dose. The trial is ongoing and 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. This ongoing research aims to further elucidate the potential of mRNA-4359 as a novel treatment approach for advanced solid tumors.
