In a small clinical trial, customized mRNA vaccines against high-risk skin cancers appeared to reduce the risk of cancer recurrence and death by nearly 50 percent over five years when compared with standard treatment alone. That’s according to Moderna and Merck, the two pharmaceutical companies that have collaborated on the experimental cancer vaccine, called intismeran autogene (mRNA-4157 or V940).
So far, the companies have only reported the top-line results in a press release this week. However, the results align closely with previous, more detailed analyses from the trial, which examined rates of recurrence and death at earlier time points, specifically at two years and three years after the treatment. More data from the trial—a Phase 2 trial—will soon be presented at a medical conference, the companies said. A Phase 3 trial is also underway, with enrollment complete.
The ongoing Phase 2 trial included 157 patients who were diagnosed with stage 3 or stage 4 melanoma and were at high risk of having it recur after surgical removal. A standard treatment to prevent recurrence after such surgery is immunotherapy, including Merck’s Keytruda (pembrolizumab). This drug essentially enables immune cells, specifically T cells, to attack and kill cancer cells—something they normally do. But, in many types of cancers, including melanoma, cancer cells have the ability to bind to receptors on T cells (called PD-1 receptors), which basically shuts the T cells down. Keytruda works by physically blocking the PD-1 receptors, preventing cancer cells from binding and keeping the T cells activated so they can kill the cancer.
In the trial, all 157 patients received Keytruda, a standard treatment. But they were randomized in a 2:1 ratio so that some would also get the customized mRNA vaccines. These vaccines were tailored specifically to each patient’s melanomas, carrying genetic instructions to build up to 34 unique markers of their mutated cancer cells. Once in the patient, healthy cells produce those markers and use them to train T cells to identify and attack the cancer cells.
mRNA’s potential
Previous data from the trial reported that 107 participants received the mRNA vaccine and Keytruda treatment, while the remaining 50 only received Keytruda. At the two-year follow-up, 24 of the 107 (22 percent) who got the experimental vaccine and Keytruda had recurrence or death, while 20 of 50 (40 percent) treated with just Keytruda had recurrence or death, indicating a 44 percent risk reduction. The companies did not report the breakdown of the two groups in the press release this week for the five-year follow-up, but said the risk reduction was 49 percent, which is also what the companies reported for the three-year follow-up.
As for side effects, the companies reported that little had changed from previous analyses; adverse events were similar between the two groups. The top side effects linked to the vaccine were fatigue, injection site pain, and chills.
The results “highlight the potential of a prolonged benefit” of the vaccine combined with Keytruda in patients with high-risk melanoma,” Kyle Holen, a senior vice president at Moderna, said.
They also “illustrate mRNA’s potential in cancer care,” he said, noting that the company has eight more Phase 2 and Phase 3 trials going for mRNA vaccines against a variety of other cancers, including lung, bladder, and kidney cancers.
Marjorie Green, a senior vice president at Merck, called the five-year follow-up data a “meaningful milestone” and “encouraging.”
“[W]e look forward to late-stage data from the INTerpath clinical development program with Moderna, across a range of tumor types where significant unmet needs remain,” she said.
While the top-line results appear positive, conclusions can’t be drawn until the full data from the trial are published. The vaccines are also being developed amid a political environment hostile to mRNA vaccines. Anti-vaccine Health Secretary Robert F. Kennedy Jr. has railed against mRNA COVID-19 vaccines, making false claims about their safety and efficacy. In August, Kennedy unilaterally canceled $500 million in grant funding for the development of mRNA-based vaccines against diseases that pose pandemic threats.
Originally published at Ars Technica
