A customized mRNA vaccine designed to fight aggressive skin cancer has delivered sustained protection over five years. Patients receiving the experimental treatment alongside standard immunotherapy saw their risk of cancer returning or dying drop by nearly 50 percent compared to those on immunotherapy alone.
Key Takeaways:
- Personalized mRNA vaccines reduced melanoma recurrence and death risk by 49% at five-year follow-up
- Each vaccine targets up to 34 unique markers from a patient's specific tumor mutations
- Moderna and Merck are now testing similar vaccines against lung, bladder, and kidney cancers
Moderna and Merck released these preliminary findings this week for their collaborative cancer vaccine, intismeran autogene (also known as mRNA-4157 or V940). The companies plan to share complete data at an upcoming medical conference. A larger Phase 3 trial has finished enrollment.
Building vaccines from tumor DNA
The Phase 2 trial enrolled 157 patients diagnosed with stage 3 or stage 4 melanoma. All had undergone surgery but faced high odds of their cancer coming back.
Every participant received Keytruda (pembrolizumab), Merck's immunotherapy drug that prevents cancer cells from disabling the immune system's T cells. Researchers randomized patients in a 2:1 ratio, with 107 also receiving the personalized mRNA vaccine.
What makes these vaccines remarkable is their customization. Scientists analyze each patient's tumor to identify up to 34 unique mutations. The vaccine then carries genetic instructions for producing markers based on those mutations. Once injected, healthy cells manufacture these markers and essentially teach T cells to recognize and destroy the cancer.
Consistent protection across years
Earlier checkpoints showed similar results. At two years, 22 percent of patients receiving both treatments experienced recurrence or death, compared to 40 percent of those on Keytruda alone—a 44 percent risk reduction. The three-year and five-year data both showed 49 percent risk reduction.
Side effects remained manageable throughout. Fatigue, injection site pain, and chills were the most common complaints, with no notable differences between treatment groups.
“These results highlight the potential of a prolonged benefit” of the vaccine combined with Keytruda in patients with high-risk melanoma, said Kyle Holen, a senior vice president at Moderna. He noted the technology extends beyond skin cancer: Moderna currently runs eight Phase 2 and Phase 3 trials testing mRNA vaccines against lung, bladder, kidney, and other cancers.
Marjorie Green, a senior vice president at Merck, called the five-year 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.
Political headwinds
These advances arrive during a complicated moment for mRNA technology. Health Secretary Robert F. Kennedy Jr. has repeatedly attacked mRNA COVID-19 vaccines with inaccurate claims about their safety and effectiveness. In August, Kennedy canceled $500 million in federal grants supporting mRNA vaccine development for potential pandemic diseases.
Full conclusions about the cancer vaccine's effectiveness must wait until researchers publish complete trial data.
Written by Alius Noreika