mRNA combination therapy produces positive results in patients with high-risk melanoma

Key takeaways:

• Messenger RNA combined with Keytruda reduced the risk for recurrence or death by 49% in patients with resected melanoma.
• The combination also reduced the risk for distant metastasis or death by 62%.

Adjuvant treatment with messenger RNA in combination with Keytruda produced meaningful improvement in patients with resected high-risk melanoma, according to findings from a phase 2b study.

When used together, messenger RNA (mRNA)-4157 (V940) (Moderna, Merck), an investigational individualized neoantigen therapy, and the anti-PD-1 therapy Keytruda (pembrolizumab, Merck), produced a “robust clinical benefit” for patients, Kyle Holen, MD, senior vice president and head of development, therapeutics and oncology at Moderna, said in a company press release.

“These data add another positive analysis to the multiple endpoints and subgroups previously assessed in this study,” Holen continued.

In the ongoing, randomized, open-label KEYNOTE-942/mRNA-4157-P201 study, 157 patients with high-risk stage 3 and 4 melanomas who underwent complete resection were assigned 2:1 to either adjuvant treatment — nine doses of 1 mg of mRNA-4157 (V940) every 3 weeks in combination with up to 18 cycles of 200 mg of Keytruda every 3 weeks — or 200 mg of Keytruda alone for 1 year until disease recurrence or unacceptable toxicity occurred.

After a median follow-up of 3 years, the combination therapy reduced the risk for recurrence or death by 49% (HR = 0.51; 95% CI, 0.288-0.906) compared with Keytruda alone.

The combination also demonstrated a meaningful improvement in distant metastasis-free survival compared with Keytruda alone, with the risk for distant metastasis or death being reduced by 62% (HR = 0.384; 95% CI, 0.172-0.858).

The safety profile remained consistent with those previously reported. The most common adverse events were fatigue (60.6%), injection site pain (56.7%) and chills (49%).

Based on these data, the FDA has granted breakthrough therapy designation and the European Medicines Agency has granted priority medicines scheme to this combination therapy for the treatment of patients with high-risk melanoma.