Adding a personalized mRNA vaccine to adjuvant treatment with pembrolizumab prolongs relapse-free survival (RFS) in patients with high-risk melanoma, according to a phase 2 study presented at the AACR Annual Meeting 2023.
The vaccine, mRNA-4157, is an individualized neoantigen therapy that encodes up to 34 neoantigens, said study presenter Jeffrey Weber, MD, PhD, of NYU Langone Health in New York, New York.
Dr Weber and colleagues tested mRNA-4157 in the phase 2 KEYNOTE-942 trial (ClinicalTrials.gov Identifier: NCT03897881). The trial enrolled 157 patients with stage IIIB-IV cutaneous melanoma who had undergone complete resection.
Patients were randomly assigned to receive mRNA-4157 plus pembrolizumab (n=107) or pembrolizumab alone (n=50). Baseline characteristics were generally well balanced between the treatment arms, but patients in the vaccine arm were more likely to have a high tumor mutational burden (≥10 mutations/Mb; 73.8% vs 60%).
Pembrolizumab was given at 200 mg every 3 weeks for up to 18 cycles, and the vaccine was given intramuscularly every 3 weeks for up to 9 doses. The median follow-up was 23 months for the vaccine arm and 24 months for the monotherapy arm.
The primary endpoint was RFS. The mRNA-4157 vaccine significantly improved RFS (hazard ratio, 0.561; 95% CI, 0.309-1.017; P =.0266). The 18-month RFS rate was 78.6% in the vaccine arm and 62.2% in the monotherapy arm. The RFS benefit with mRNA-4157 was seen regardless of PD-L1 status.
Treatment-related adverse events (TRAEs) occurred more frequently in the vaccine arm than in the monotherapy arm. The rate of grade 3 or higher TRAEs was 25% in the vaccine arm and 18% in the monotherapy arm. The grade 3 or higher vaccine-related events were fatigue (4.8%), pyrexia (1%), and myalgia (1%).
Data on distant metastasis-free survival are expected to be presented at the ASCO Annual Meeting this year, and an update on RFS could be presented as early as the ESMO Congress, Dr Weber said. He added that a phase 3 study of mRNA-4157 plus pembrolizumab is expected to begin this summer.
Disclosures: This research was supported by Moderna, Inc. in collaboration with Merck Sharp & Dohme, LLC. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Khattak A, Carlino M, Meniawy T, et al. A personalized cancer vaccine, mRNA-4157, combined with pembrolizumab versus pembrolizumab in patients with resected high-risk melanoma: Efficacy and safety results from the randomized, open-label Phase 2 mRNA-4157-P201/Keynote-942 trial. AACR 2023. April 14-19, 2023. Abstract CT001.