The companies have an expansive clinical program for the mRNA neoantigen therapy intismeran autogene in combination with immuno-oncology heavyweight Keytruda.
Merck and Moderna’s mRNA neoantigen therapy reduced the risk of recurrence or death in patients with advanced melanoma by nearly half at the five-year mark of a mid-stage trial when paired with Keytruda. The latest results build on the companies’ efforts to develop a long-term solution to the intractable skin cancer that often recurs even after complete removal via surgery.
The data come from an analysis of the Phase IIb KEYNOTE-942/mRNA-4157-P201 study, an open label trial that paired the therapy, called intismeran autogene, with Merck’s immuno-oncology juggernaut. Patients had high-risk stage three or four melanoma and underwent complete resection prior to receiving the treatment combo or Keytruda alone for a year.
In a readout at the three-year mark in December 2023, the combo reduced the risk of recurrence or death by 49% compared to Keytruda alone.
In Tuesday’s release, the companies said that number was the same at the five-year mark. They did not report what Keytruda alone achieved. The study originally reached the primary endpoint in December 2022, achieving a risk reduction of 44%.
Moderna and Merck said in a statement that the data builds on the analyses performed at two years and three years. Safety was consistent with previous readouts.
“While incremental,” William Blair analysts wrote in a note Tuesday morning, “we view today’s 5-year data update on intismeran as positive maintenance of an impressive effect over Keytruda monotherapy, the first therapy, to our knowledge, to show added benefit in this post-surgical setting.”
Jefferies meanwhile saw the data reading through positively towards Moderna’s goal of hitting breakeven by 2028. “While [intismeran autogene] could reach the market as early as 2027,” analysts at the firm wrote in a Tuesday note, “the 50:50 collaboration agreement with MRK could result in more meaningful sales in 2028, around MRNA’s breakeven guidance by 2028.”
Intismeran autogene, previously known as mRNA-4157, is a therapeutic vaccine that aims to boost the efficacy of the immune system in fighting cancer. The vaccine is designed to generate T cell responses targeted to the patient’s specific tumor.
The companies are working on a fully enrolled Phase III trial for the combo as an adjuvant treatment in melanoma, while enrollment is underway for a Phase III test in lung cancer, a Phase II test in renal cell carcinoma and more.
Editor’s Note: This story was edited at 10 a.m. ET on January 20, 2026, to clarify the joint development of mRNA-4157. Additional context from analysts was also added at 10:30 a.m. ET.
