Perlmutter Cancer Center Clinical Trial Tests Personalized mRNA Vaccine for Treating Metastatic Melanoma

A large-scale international phase 3 clinical trial is evaluating the effectiveness of combining the immunotherapy drug pembrolizumab with V940, a personalized, experimental mRNA vaccine, to treat people with metastatic melanoma. The trial is led at NYU Langone by Jeffrey S. Weber, MD, PhD, deputy director of Perlmutter Cancer Center.

V940 trains the immune system to attack proteins called neoantigens that are specific to a patient's tumor and not found in normal tissue. Researchers sequence the patient's tumor to create a vaccine customized for their cancer that targets up to 34 of the neoantigens. An earlier phase 2b trial tested the combination of V940 and pembrolizumab in 107 patients who had had surgery to remove melanoma from lymph nodes or other organs and were at high risk of the disease returning in sites distant from the original cancer. In 24 subjects of 107 (22.4 percent), melanoma returned within three years of follow-up, compared with 20 out of 50 (40 percent) of those who received only pembrolizumab.

Based on these results, the U.S. Food and Drug Administration granted Breakthrough Therapy Designation to V940 in combination with pembrolizumab for the adjuvant treatment of patients with high-risk melanoma.

The recently launched randomized, double-blind phase 3 study aims to enroll more than 1,000 participants in multiple sites across the United States and Australia, with up to 85 months of follow-up planned.

"While the results of the phase 2b study are encouraging, additional data in both neoadjuvant and adjuvant settings are needed to contextualize these findings and V940's potential role," said Dr. Weber, who also is the Laura and Isaac Perlmutter Professor of Oncology in the Department of Medicine at NYU Grossman School of Medicine. "This phase 3 study will provide a more comprehensive and definitive assessment of the long-term safety and efficacy of the combination of V940 and pembrolizumab as an adjuvant treatment for resected high-risk melanoma."