In December 2022 Moderna and Merck announced positive results from a Phase IIb trial of mRNA-4157/v940, an investigational personalised cancer vaccine, in combination with Merck’s anti-PD-1 therapy KEYTRUDA. In this trial, the combination approach demonstrated a “statistically significant and clinically meaningful improvement” in the primary endpoint of “recurrence-free survival (RFS)” compared to KEYTRUDA alone for the treatment of patients with stage III/IV melanoma following complete resection.
mRNA makes waves
As we explored in October 2022, mRNA progress against cancer is hotly anticipated after its success in COVID-19 vaccination strategies. This candidate, mRNA-4157/V940, is a novel personalised cancer vaccine comprising a “single synthetic mRNA coding for up to 34 neoantigens”. This is designed and developed from the “unique mutational signature of the DNA sequence of the patient’s tumour”.
“Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a key step in adaptive immunity.”
The process and the trial
Stéphane Bancel, CEO of Moderna, published a blog post in which he described the process behind developing personalised cancer vaccines. He stated that study participants have blood drawn and tumours biopsied before lab sequencing. This presents a comparison between the biopsy sample and healthy blood cells, to “identify the unique genetic mutations” of that person’s cancer.
The next stage involves a “proprietary algorithm developed in collaboration with Merck”, which reviews the mutations and predicts up to 34 that are suspected to help the immune system recognise and “attack” tumour cells.
“Next, the investigational personalised mRNA cancer vaccine is created to give cells instructions to make the ‘fingerprint’ cancer protein”.
The vaccine is then manufactured and shipped to the trial site. Patients were injected with their vaccines in order to investigate the effects of combination treatment with KEYTRUDA, compared to KEYTRUDA alone. KEYTRUDA is “considered a standard of care in adjuvant melanoma”. The results were positive: “adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44%”.
Good for the field
Mr Bancel stated that the results are “highly encouraging for the field of cancer treatment”. He indicated that the next steps involve “additional studies in melanoma and other forms of cancer”. The goal is to bring “truly individualised cancer treatments to patients”.
Dr Dean Y. Li is President of Merck Research Laboratories and described the “positive findings” as an “important milestone in our collaboration with Moderna”. The joint statement from the companies looks forward to discussing the results with regulatory authorities and the initiation of a Phase III study melanoma patients in 2023.
To hear more from both Moderna and Merck at the World Vaccine Congress in Washington next year, get your tickets today.