In an investor news release from December 2023, Moderna and Merck shared follow-up data from the Phase 2b KEYNOTE-492/mRNA-4157-P201 clinical trial. During the trial, researchers explored the impact of Keytruda (pembrolizumab) in conjunction with an investigational vaccine called mRNA-4157 (V940) for the treatment of high-risk melanoma (stages 3 or 4). In particular, patients in the trial had their melanoma surgically resected, or surgically removed. So what is mRNA-4157 (V940)? This investigational mRNA individualized neoantigen therapy is personalized based on the specific mutational signature of each patient’s tumor, allowing for more targeted treatment.

157 participants enrolled in the study. Participants were split into two cohorts. The first cohort received mRNA-4157 (V940) alongside Keytruda, whereas the second cohort received only Keytruda. Researchers aimed to understand how the combination impacted recurrence-free survival rates, how safe the treatment(s) were, and distant metastasis-free survival. After three years of follow-up data was collected, the researchers found that:

• The combination treatment reduced melanoma recurrence and/or mortality risk by approximately 49%. Additionally, the combination treatment reduced the risk of distant metastasis (the melanoma metastasizing, or spreading, to distant areas of the body) or death by 62% when compared to Keytruda as a monotherapy.
• Keytruda and mRNA-4157 (V940) were found to be relatively safe and well-tolerated. While some severe side effects did occur, the most common side effects were relatively mild. The highest reported side effects were injection site reactions, chills, and fatigue.

The combination treatment has earned Breakthrough Therapy and PRIME designations in the U.S. and E.U. respectively. Moving forward, Merck and Moderna are continuing to hold a Phase 3 study to further evaluate this therapeutic combination in individuals living with resected melanoma. Additional studies are exploring the combination treatment in other indications.

What to Know: Melanoma

Melanoma is considered the most severe form of skin cancer and forms in melanin-producing cells called melanocytes. While it can occur in children, this cancer is most common in adults. It is often found on the head, neck, or the area between the shoulders and hips in men, or on the arms and legs in women. However, melanoma can spread to other areas of the body. During diagnosis, doctors will stage your melanoma. In stage I, the melanoma is small and hasn’t spread past its original manifestation. By stage II, the melanoma has grown in size. Stage III means that the melanoma has spread to the lymph nodes, and stage IV is when the cancer has spread to other organs. Cases of melanoma have been increasing over the past 30 years.

So how can you determine if a spot on your skin is melanoma? Consider ABCDE to decide.

A is asymmetrical shape. If you have a mole that is misshapen, or one part doesn’t match the other, it could signify melanoma.

B is irregular border. Does your mole have notched, ragged, or irregular borders? This may mean that it is abnormal.

C represents changes in color. Normal moles are often one color, such as brown or black. If your mole has many different colors within it, it could be melanoma.

D stands for diameter. Normal moles are often smaller in size. A melanoma spot may be larger than 1/4 inch.

Finally, E represents evolving, or a mole that changes in size or color over time, begins to itch, or bleeds.

People with darker skin are more likely to develop melanoma in hidden areas like under the nails or in the digestive tract, eyes, or mouth. Alternately, people with lighter skin often develop melanomas in areas of high sun exposure.

Melanoma treatment varies but may include chemotherapy, targeted therapy, radiation, or surgery. If you have melanoma, please speak with your doctor about the best course of treatment.