- About half of the people treated for melanoma will have a recurrence.
- Researchers recently presented phase 2b clinical trial results showing a combination of an mRNA vaccine and immunotherapy helps reduce the likelihood of melanoma recurrence in people who had surgery to remove melanoma from lymph nodes or other organs.
- The researchers combined the experimental vaccine mRNA-4157/V940 and the immunotherapy pembrolizumab in patients with melanoma.
In 2020, almost 325,000 people globally were diagnosed with melanoma — a type of skin cancer.
Previous research says the number of people with melanoma will increase to 510,000 cases worldwide by 2040.
Past studies show about half of people treated for melanoma will have a recurrence, with about 50% of them occurring in the lymph nodes and about 30% in other areas of the body.
Researchers recently presented phase 2b clinical trial results at the annual meeting of the American Association for Cancer Research, showing a combination of an experimental mRNA vaccine with immunotherapy helps reduce the likelihood of melanoma recurrence in people who had surgery to remove melanoma from lymph nodes or other organs and were at high risk for recurrence.
The clinical trial was funded by Moderna Inc., which makes the experimental vaccine mRNA-4157/V940, and Merck, which manufactures the immunotherapy drug pembrolizumab.
What is melanoma?
Melanoma is a type of skin cancer that can occur anywhere on the body’s skin. The cancer develops when human skin cells called melanocytes start to divide and grow out of control.
The most common cause of melanoma is exposure to ultraviolet (UV) light from the sun. Scientists also believe genetic factors may also be involved.
People at risk for melanoma tend to have a fair complexion that burns easily. Other melanoma risk factors include:
- having blonde or red hair
- blue or green eyes
- skin that freckles easily
- weakened immune system
- age
- gender
There are five stages of melanoma, starting at Stage 0 where the cancer is only present in the outermost skin layer, and up to Stage 4 where the cancer has spread to other parts of the body.
Symptoms of melanoma are generally changes spotted on your skin. These can include:
- a new spot or mole
- a change in the color, shape, or size of an existing spot or mole
- a skin sore that does not heal
- a skin spot that becomes itchy, painful, and/or bleeds
- a skin spot that looks very shiny
- a firm, red spot that looks dry or crusty and may bleed
The most common treatment for melanoma is surgery where the cancerous area is removed. Additionally, radiation therapy, chemotherapy, or immunotherapy may also be used depending on the case.
Combining a vaccine and immunotherapy
According to Dr. Jeffrey Weber, deputy director of the Laura and Isaac Perlmutter Cancer Center and senior investigator of this research, there were two main reasons why they decided to combine the experimental vaccine mRNA-4157/V940 with immunotherapy, in this case, pembrolizumab.
“The existing standard adjuvant therapy was a PD-1 antibody such as pembrolizumab, which is the reference control arm, and neoantigen vaccines have been shown to have promise to generate immune responses against neoantigens, which are felt to be clinically important,” he explained to Medical News Today.
“The addition of PD-1 blockade also would promote the activity of the resulting neoantigen-specific T cells induced by the vaccine,” he added.
Targeting cancer with vaccines
And although immunotherapies have become the mainstay for treating melanoma, they do not work for all patients because melanoma cells, known for their ability to evade the immune system, can become resistant to immunotherapy, said Dr. Andrew L. Pecora, hematologist/oncologist at Hackensack Meridian Health and one of the co-authors of this study.
“For this reason, researchers have looked at adding vaccines,” he told MNT.
“While most vaccines used today are designed to prevent infections, they can also be tailored to target proteins involved in cancer. Like the COVID-19 vaccine, mRNA-4157/V940 is based on messenger RNA, a chemical cousin of DNA that provides instructions to cells for making proteins.”
— Dr. Andrew L. Pecora
“mRNA cancer vaccines are designed to teach the body’s immune system to recognize cancer cells as different from normal cells. In designing a vaccine against melanoma, researchers attempted to trigger an immune response to specific abnormal proteins, called ‘neoantigens,’ made by cancer cells,” Dr. Pecora continued.
Studying the results
For this phase 2b clinical trial, Dr. Weber and his team injected 107 study participants with both the experimental mRNA vaccine and the immunotherapy pembrolizumab.
An additional 50 participants only received pembrolizumab.
Upon analysis, researchers found melanoma redeveloped in 24 of the participants within two years of follow-up (22.4%), compared to 20 out of 50 people (40%) who received only pembrolizumab.
“The vaccine stimulated immune T cells to recognize neoantigens on the tumor and not normal cells,” Dr. Weber explained how the combination therapy works.
“The pembrolizumab disinhibits the resulting cells, making them longer-lived and more effective killer cells,” he explained.
The researchers reported the most common side effect of the combination therapy was fatigue.
“Similar types of side effects as seen with pembrolizumab alone, with the addition of the expected side effects of the vaccine, mainly fevers, chills, muscle aches, and fatigue that lasts a day or two,” Dr. Weber said.
“The majority of the vaccine-related side effects are what we call low-grade, not disabling,” he added.
Melanoma vaccine: Moving to phase 3
Dr. Weber said they plan to start a phase III randomized study by this summer to definitively demonstrate the clinical benefit of adding a neoantigen mRNA vaccine to PD-1 blockade as adjuvant therapy for high-risk resected melanoma.
“If the phase II study starts this summer, it will take two years for data to emerge, and at least another three to six months to assemble a BLA from Merck-Moderna and another six months for the FDA to make a decision,” he said when asked when we might see this combination therapy available for doctors to use.
“Figure maybe three years from this summer. It could be shorter, but not likely much longer,” he said.
Next level of immunotherapy
As a doctor who treats people with melanoma, Dr. Pecora said this research is opening the field to take immunotherapy to the next level.
“Currently, immunotherapy works about half the time. This will significantly increase the number of patients who will benefit from immunotherapy because, with mRNA technology, you can actually educate the patient’s immune system to recognize and attack their specific type of cancer,” he said.
Medical News Today also spoke with Dr. Trevan Fischer, a surgical oncologist and assistant professor of surgical oncology for Saint John’s Cancer Institute at Providence Saint John’s Health Center in Santa Monica, CA, about this clinical trial.
He said this was exciting data that shows where melanoma treatment is headed.
“For about 10 or 15 years, we’ve had [i]mmunotherapies. They worked on their own and so the next phase of that is to try to figure out how we can add other therapies that may or may not have worked on their own, but add them to these now standard-of-care therapies to see if we can get even more response, which is what this study showed,” Dr. Fischer explained.
He also said it is important to have therapies available for people who had a melanoma removed from lymph nodes or other organs as they are at a higher risk for disease recurrence.
“Trying to prevent a recurrence could be the most important part once you’ve had a melanoma because if it recurs in a lymph node next to where you’ve already operated, that may not be that big of an operation. But if it recurs in a very important part of the brain or in a part next to an important (blood) vessel, the treatment options are much more limited.”
— Dr. Trevan Fischer
“So these types of studies in this setting (are) all about minimizing recurrences and hopefully to someday prevent them altogether,” he added.
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