An mRNA Melanoma Vaccine Shows Promise

Moderna says the same mRNA Technology that fueled its COVID-19 vaccine is proving effective in fighting melanoma.

The company presented the latest results from its trial involving 157 people with advanced skin cancer at the annual meeting of the American Society of Clinical Oncology in Chicago. In the study, Moderna and Merck combined their cancer treatments—Moderna’s experimental cancer vaccine and Merck’s approved checkpoint inhibitor pembrolizumab (Keytruda)—to achieve potentially life-changing results for melanoma patients.

In the phase 2 study of patients with stage 3 or stage 4 melanoma who were treated after surgery to remove the bulk of their tumors, two thirds received a monthly dose of Moderna’s cancer vaccine for nine months, along with pembrolizumab treatments every three weeks for a year. The remaining one third received pembrolizumab alone.

After about three years, those who had received the two treatments had a 49% lower risk of cancer recurrence or death, and a 62% lower risk of their cancer spreading, compared to people who got only pembrolizumab. Overall, 75% of the patients taking the two therapies survived with no recurrences at 2.5 years, compared to 56% of those on pembrolizumab.

“Across all measures of efficacy, we are starting to see significant and durable responses,” says Dr. Stephen Hoge, president of Moderna. “This is a dramatic impact on melanoma.”

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The cancer vaccine relies on the same mRNA Technology behind the COVID-19 vaccine, a molecular plug-and-play platform that makes it possible to swap out genetic information coding for different proteins that can be created relatively quickly. Each of the treated patients received a custom-made vaccine, which took six to eight weeks to develop, that was tailored to the specific mutations in their tumor. “The results give us an extremely high degree of confidence that this effect is real and very long lasting,” says Hoge. “We think at this point it’s incredibly clear that these strong results will change cancer treatment in the years ahead.”

The other drug used in the study, pembrolizumab, launched a new era of immunotherapy treatments when it was approved in 2014. It unmasked tumor cells and made them more visible for attack by the immune system. The new study shows that combining two immune-based strategies—priming the immune system with a vaccine to generate T cells designed to recognize and destroy tumor cells, along with a drug that exposes tumor cells—can be a powerful way to control malignant growth.

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Hoge says the company’s studies show that the treatment increases populations of T cells that specifically target the tumors. Each patient’s vaccine includes up to 34 tumor-specific targets, and most patients generated strong T cell populations against 15 to 20 of them. “We are hitting [the tumor] with a large number of T cells, and targeting not just one mutation, but often 15 of them, so there aren’t many places [for the tumor] to hide,” says Hoge. “It’s a very broad immune response.”

The trial will continue to follow these patients and will include 100 more in phase 3. The two companies are also testing the same combination in patients with another type of skin cancer, squamous cell carcinoma, both before and after surgery, as well as in kidney and bladder cancer patients. If the current results hold up, they could represent a milestone for cancer immunotherapy, potentially opening the door for a one-time treatment that might eliminate a person's cancer for good. “If these survival curves continue beyond three years, then it looks like we have effectively eliminated the tumor cells,” says Hoge. “Even if there is a single cell somewhere that hides out for a couple of years and then tried to get going again to form another tumor, the immune system already has its mug shot, and knows what it looks like—so the moment it commits its next crime, the immune system clears it up."

"This combination ramps up the immune response to effectively stamp out the cancer," he says, "and once it’s gone, it’s gone.”