mRNA cancer vaccine combined with Keytruda promising in adjuvant treatment of melanoma

mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, with Keytruda met the primary endpoint of recurrence-free survival in a phase 2b trial for the adjuvant treatment of stage III/IV melanoma after surgical resection.

“This is a pivotal moment because it is really the first vaccine and mRNA technology that has been able to show clinical benefit in a randomized setting against an active comparator,” Michelle Brown, MD, PhD, program director for oncology at Moderna, said in a press conference discussing the results.

“What’s just really fascinating about this treatment is it’s unlike any other treatment that exists today by that it is truly personalized to an individual’s cancer,” Kyle Holen, MD, head of development for oncology at Moderna, said in the press conference.

The KEYNOTE-942 randomized clinical trial investigated the efficacy of the mRNA vaccine in combination with Keytruda (pembrolizumab, Merck) compared with Keytruda alone, according to a joint press release from Moderna and Merck. The trial enrolled 157 patients with stage III/IV melanoma who had undergone complete surgical resection, were disease free at study entry and had a high risk for recurrence. Participants were randomly assigned to receive a combination of mRNA-4157/V940 (nine doses) and Keytruda (200 mg every 3 weeks up to 18 cycles) or Keytruda alone for approximately 1 year until disease recurrence or unacceptable toxicity.

The combination demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of recurrence-free survival vs. Keytruda alone, reducing the risk for recurrence or death by 44% (HR = 0.56; 95% CI, 0.31-1.08; one-sided P = .0266).

“In regards to safety, patients had the type of adverse events that they would expect with Keytruda alone,” Brown said. “Unlike other combinations that have been tested in this phase, we didn’t see an increase in these sorts of adverse events. Each one was really a unique profile.”

Moderna and Merck plan to discuss the results with regulatory authorities, work toward publishing the full data set and initiate a phase 3 study in patients with melanoma in 2023.

“We do plan on launching additional clinical trials not only in melanoma but in other tumor types because, as we’ve heard, this is a personalized cancer vaccine, and so it’s not just for melanoma patients. It could potentially be for patients with all sorts of other tumors,” Brown said.

“We have a very robust pipeline in oncology,” Holen said. “Moderna is likely not known as an oncology company, but I assure you, we will be known as an oncology company.”