16 November 2017 - - Cambridge, Massachusetts-based messenger RNA therapeutics and vaccines developer Moderna Therapeutics has begun dosing patients in a Phase 1 study of mRNA-4157, an mRNA-based personalized cancer vaccine, the company said.
The Phase 1 open-label, dose escalation, multicenter study (KEYNOTE-603), expected to enroll up to 90 patients across multiple clinical study sites in the United States, will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors, and in combination with Keytruda (pembrolizumab), an anti-PD-1 therapy, marketed by Merck (known as MSD outside the US and Canada) in subjects with unresectable solid tumors.
The first-in-human dosing of mRNA-4157 marks a key milestone in the strategic collaboration between Moderna and Merck to advance the novel mRNA-based personalized cancer vaccine in combination with Keytruda for the treatment of multiple types of cancer.
Moderna is creating individualized, mRNA-based personalized cancer vaccines through next-generation sequencing that identifies mutations found on a patient's cancer cells, called neoepitopes. Neoepitopes can help the immune system distinguish cancer cells from normal cells.
Using algorithms developed by its in-house bioinformatics team, Moderna predicts 20 neoepitopes present on the patient's cancer that should elicit the strongest immune response, then creates a vaccine that encodes for each of these mutations and loads them onto a single mRNA molecule.
Once injected into the patient, the vaccine should direct the patient's cells to express the selected neoepitopes, which may help the patient's immune system better recognize cancer cells as foreign and destroy them.
mRNA-4157 also has the potential to enhance clinical outcomes associated with checkpoint inhibitor therapies. In 2016, Moderna and Merck formed a collaboration to develop mRNA-4157 in combination with Merck's anti-PD-1 therapy, Keytruda.
The development program will entail multiple studies in several types of cancer and include the evaluation of mRNA-4157 in combination with Keytruda.
Privately held Moderna is developing mRNA vaccines and therapeutics as a new class of medicines for infectious diseases, cancer (immuno-oncology), rare liver diseases, cardiovascular and pulmonary diseases, through proprietary development and collaborations with strategic partners.