EMA Awards PRIME Scheme Designation to mRNA-4157/V940 Plus Pembrolizumab in High-risk Melanoma

The European Medicines Agency (EMA) has granted Priority Medicines (PRIME) scheme designation to the personalized cancer vaccine mRNA-4157/V940 and pembrolizumab (Keytruda) for use as adjuvant treatment in patients with high-risk, stage III or IV melanoma following complete resection.¹

PRIME supports the development of medicines that target an unmet medical need. Through this designation, the EMA offers early and proactive support to augment the generation of robust data on the risk and benefits of a therapeutic approach and speed up the development and evaluation of drug applications to help patient benefit from life-changing treatments as early as possible.

The regulatory decision is supported by findings from the phase 2b KEYNOTE-942 trial (NCT03897881), in which the combination resulted in a statistically significant and clinically meaningful 44% reduction in the risk of disease recurrence or death vs single-agent pembrolizumab in this population (HR, 0.56; 95% CI, 0.31-1.08; P = .0266).²

Detailed results from the study will be presented at the upcoming 2023 AACR Annual Meeting.

“Prime scheme designation for mRNA-4157/V940 in combination with [pembrolizumab] highlights the potential promise of individualized cancer treatments in a population with limited alternatives,” Stephen Hoge, MD, president of Moderna, Inc., stated in a press release. “There is a high unmet need for therapies in melanoma, as it can be a life-threatening condition where available therapies may not be sufficiently effective in a significant proportion of patients.”

mRNA-4157/V940 is comprised of a single synthetic mRNA that codes for up to 34 neoantigens; it is designed and produced based on the unique mutational signature of the patient’s tumor. After the vaccine has been administered to the patient, mRNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation which is necessary to provide adaptive immunity.

Data from early clinical studies have suggested that the addition of pembrolizumab to mRNA-4157/V940 could result in additive benefit and serve to strengthen the T-cell–mediated elimination of cancer cells.

The randomized, open-label, phase 2b KEYNOTE-942 trial enrolled patients with high-risk resectable cutaneous melanoma.³ They were required to have an ECOG performance status of 0 or 1 and acceptable organ and marrow function. Patients must have undergone complete resection within 13 weeks before their first dose of pembrolizumab would be received on study. Following resection, they needed to be free of disease at the time of study entry without locoregional relapse or distant metastasis.

Those with brain metastases were excluded from the research.

A total of 157 patients were randomly assigned to receive 9 total doses of mRNA-4157/V940 plus pembrolizumab at 200 mg every 3 weeks for up to 18 cycles for about 1 year vs pembrolizumab monotherapy for the same duration until recurrence or intolerable toxicity.¹

Recurrence-free survival serves as the primary end point of the trial, and key secondary end points include distant metastasis-free survival and safety.

“The milestone underscores the potential for personalized approaches to help improve outcomes for people living with certain types of melanoma,” Eric H. Rubin, MD, senior vice president of global clinical development at Merck Research Laboratories, stated in a press release. “We look forward to working with the EMA, in collaboration with Moderna, to advance our clinical development program for mRNA-4157/V940 in combination with [pembrolizumab].”

Previously, in February 2023, the FDA granted a breakthrough therapy designation to the investigational personalized mRNA cancer vaccine plus pembrolizumab for the same adjuvant indication in patients with high-risk melanoma after complete resection.⁴ Data from KEYNOTE-942 also supported this designation.

References

1. mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with Keytruda (pembrolizumab), receives PRIME scheme designation from the European Medicines Agency for adjuvant treatment of patients with high-risk stage III/IV melanoma following complete resection. News release. Merck. April 7, 2023. Accessed April 7, 2023. https://www.merck.com/news/
2. Moderna and Merck announce mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with Keytruda (pembrolizumab), met primary efficacy endpoint in phase 2b KEYNOTE-942 trial. News release. Merck. December 13, 2022. Accessed April 7, 2023. https://www.merck.com/news/
3. An efficacy study of adjuvant treatment with the personalized cancer vaccine mRNA-4157 and pembrolizumab in participants with high-risk melanoma (KEYNOTE-942). ClinicalTrials.gov. Updated August 24, 2022. Accessed April 7, 2023. https://clinicaltrials.gov/ct2/show/NCT03897881
4. Moderna and Merck announce mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with Keytruda^® (pembrolizumab), was granted breakthrough therapy designation by the FDA for adjuvant treatment of patients with high-risk melanoma following complete resection. News release. Moderna. February 22, 2023. Accessed April 7, 2023. https://www.merck.com/news/