Personalized Cancer Vaccine + Pembrolizumab Designated Breakthrough Tx for Melanoma

The Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with pembrolizumab (Keytruda^®), a programmed death receptor-1 (PD-1)-blocking antibody, for the adjuvant treatment of patients with high-risk melanoma following complete resection.

The vaccine candidate consists of a single synthetic mRNA coding for up to 34 neoantigens. It is designed to stimulate an immune response by generating specific T cell responses based on the unique mutational signature of a patient’s tumor.

The designation is supported by data from the randomized, open-label phase 2 KEYNOTE-942 study (ClinicalTrials.gov Identifier: NCT03897881), which compared the efficacy and safety of mRNA-4157/V940 plus pembrolizumab to pembrolizumab alone in patients with stage III/IV melanoma following complete resection (N=157).

Findings showed that mRNA-4157/V940 in combination with pembrolizumab statistically significantly reduced the risk of disease recurrence or death by 44% compared with pembrolizumab alone (hazard ratio, 0.56 [95% CI, 0.31-1.08]; 1-sided P =.0266).

“The FDA’s Breakthrough Designation for mRNA-4157/V940 in combination with Keytruda reflects the excitement that we have for the potential promise of individualized cancer treatments,” said Stephen Hoge, MD, Moderna’s President. “mRNA-4157/V940 in combination with Keytruda provided the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and potentially represents a new frontier in treating melanoma and other cancers.”

A phase 3 study in adjuvant melanoma is expected to begin this year. The Companies also plan to expand the research into other tumor types, including non-small cell lung cancer.

Keytruda is currently approved for the treatment of patients with unresectable or metastatic melanoma. It is also indicated for the adjuvant treatment of patients 12 years of age and older with Stage IIB, IIC, or III melanoma following complete resection.

References

1. 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 and Merck. February 22, 2023. Accessed February 23, 2023. https://www.merck.com/news/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/.
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. Moderna and Merck. December 13, 2022. Accessed February 23, 2023. https://www.merck.com/news/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-94/.