Moderna’s personalised messenger RNA (mRNA)-based cancer vaccine mRNA-4157 in combination with Merck & Co’s Keytruda was granted Priority Medicines scheme designation by the EMA on 6 April 2023.

It was also granted Breakthrough Therapy Designation by the FDA in February 2023 for the adjuvant treatment of patients with high-risk stage III/IV melanoma following complete resection based on the results of the open-label, randomised, Phase IIb KEYNOTE-942 trial.

The findings, which were presented at the 2023 American Association for Cancer Research (AACR) Annual Meeting, held from 14-19 April, showed that mRNA-4157 in combination with Keytruda improved recurrence-free survival (RFS) compared with Keytruda alone when used as an adjuvant treatment in patients with resected high-risk melanoma, regardless of tumour mutational burden.

The overall 18-month RFS rate was 78.6% (95% confidence interval [CI], 69.0-85.6%) with the combination versus 62.2% (95% CI, 46.9-74.3%) with Keytruda alone, leading to a 44% reduction in the risk of disease recurrence or death (hazard ratio [HR], 0.561; 95% CI, 0.309-1.017; 1-sided P = 0.0266).

As part of the trial, patients’ tumour inflammation score (TIS) and PD-L1 expression were measured. By design, mRNA-4157 is made to target a patient’s unique tumour mutations, with individualised mRNA encoding for up to 34 neoantigens.

The RFS benefit with the combination versus single-agent Keytruda was observed in TIS-high tumours (HR, 0.576; 95% CI, 0.209-1.591) and TIS-non-high tumours (HR, 0.528; 95% CI, 0.253-1.101). The HR was 0.485 (95% CI, 0.226-1.039) in PD-L1 positive tumours, and was 0.162 (95% CI, 0.038-0.685) in PD-L1-negative tumours.

The positive outcome of the KEYNOTE-942 trial opens the way to personalised cancer vaccines as a new approach to improve outcomes for high-risk melanoma patients with limited treatment options. In their February press release, Moderna and Merck announced the plan to start a Phase III clinical trial of the mRNA-4157-Keytruda combination in melanoma patients in 2023.

The combinations are also under development for other oncology indications, including non-small cell lung cancer and head and neck squamous cell carcinoma, indicating the potential for a broad application of the therapy across multiple indications. In terms of the pipeline asset’s potential market opportunity, GlobalData’s Consensus Analyst Forecast database projects sales for mRNA-4157 to reach $291m by 2028.