Combination mRNA cancer vaccine and Keytruda sustains recurrence-free survival at five years

Metastatic melanoma cells – Image Credit National Cancer Institute

CANCER DIGEST – Jan. 24, 2026 – When a personalized mRNA cancer vaccine is added to an immunotherapy for the treatment of advanced melanoma, more patients survived without recurrence than those treated with pembrolizumab (Keytruda®) alone, the five-year updated results of a clinical trial show.

The KEYNOTE-942 ongoing clinical trial (NCT03897881) compares the effectiveness of treatment of patients with stage 3 or higher melanoma tumors that a have been surgically removed and then treated with a personalized mRNA vaccine that takes into account 34 patient-specific tumor characteristics combined with Keytruda, versus patients treated with Keytruda alone after surgery. The updated results were announced Jan. 20, 2026 in a joint press release from Merck, makers of Keytruda, and Moderna, maker of the mRNA vaccine. 

In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be over 100,000 new cases of melanoma diagnosed and over 8,000 deaths resulting from the disease in the U.S. in 2025, according to the American Cancer Society. 

Led by Jeffrey Weber, MD, PhD, at NYU Langone Health in New York, the study began in 2019 and has enrolled 157 patients at 23 participating cancer centers in the US and Australia. Three-year results of the study were published in the Feb. 20, 2024 journal The Lancet. 

The five-year updated results show that patients treated in the vaccine arm sustained a lower rate of the cancer spreading to other parts of the body, called distant metastasis-free survival (DMFS) than the Keytruda-alone group. The DMFS rate was 89.3 percent in the vaccine arm compared to 68.7 percent of those in the Keytruda-alone group who remained metastasis free at the 30 month mark. The difference represents a 49 percent reduction in risk of recurrence or death. 

“Now with five years of follow-up data, today’s results highlight the potential of a prolonged benefit of the intismeran autogene (mRNA vaccine) and KEYTRUDA combination in patients with resected high-risk melanoma,” said Kyle Holen, M.D. in the press release. He is Moderna’s senior vice president and head of development for Oncology and Therapeutics. 

The companies are currently enrolling patients in a large phase 3 comparison trial (NCT05933577) to further test the effectiveness of the mRNA/immunotherapy combination treatment. The companies plan to enroll over 1,000 patients at 165 cancer centers around the world.

“We continue to invest in our platform in oncology because of encouraging outcomes like these, which illustrate mRNA’s potential in cancer care," Holen continued. "We look forward to several additional milestones to come, including the results of our Phase 3 study in adjuvant melanoma in collaboration with Merck, and continued progress across the eight Phase 2 and Phase 3 studies in multiple tumor types and patient populations.” 

Editor’s note: While Merck and Moderna are hoping to meet regulatory requirements needed for approval to market the combination vaccine-immunotherapy by 2027, a cloud of doubt has been cast by the cancellation of $500 million in funding for mRNA research by US Health and Human Services Secretary Robert F. Kennedy Jr. That action was praised by the FDA’s lead biologics regulator, Vinay Prasad, who called RFK Jr’s decision "wise."

Sources: Merck, Moderna joint press release, The Lancet and Clinical Trials Arena