Phase 2 Data of Personalized Cancer Vaccine With Adjuvant Pembrolizumab for Resected High-Risk Melanoma

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Earlier this week, the American Association for Cancer Research (AACR) Annual Meeting 2023 kicked off in Orlando, Florida. The 6-day conference covers a wide variety of cancer sciences and medicine topics across multiple session tracks. Today, new phase 2 safety and efficacy data was presented at AACR 2023 on mRNA-4157 (V940; Merck and Moderna), a personalized cancer vaccine combined with pembrolizumab (Merck), an anti-PD-1 therapy, as adjuvant treatment for high-risk melanoma.¹

The presentation abstract noted that targeting of mutation-derived epitopes, or neoantigens, by T cells has been shown to drive anti-tumor immune responses. MRNA-4156 encodes up to 34 patient-specific tumor neoantigens. Merck and Moderna have partnered together to determine if mRNA-4157 can be paired with adjuvant pembrolizumab to improve recurrence free survival in patients with resected stage IIIB/IIIC/IIID/ and IV melanoma.

During the randomized, open-label, phase 2 KEYNOTE-942 (NCT03897881) clinical trial, 107 patients received mRNA-4157 combined with pembrolizumab and 50 patients received pembrolizumab monotherapy. Recurrence or death was reported in 24 out of 107 patients (22.4%) in the combination arm and in 20 out of 50 patients (40%) in the monotherapy arm, with a median follow-up of 101 and 105 weeks. The 18-month recurrence free survival rates (95% CI) were 78.6% (69.0% at 101 weeks and 85.6% at 105 weeks) in the combination arm and 62.2% (46.9% at 101 weeks and 74.3% at 105 weeks) in the monotherapy arm.

The combination arm showed protocol defined statistical significance and a clinically meaningful improvement in recurrence free survival compared to pembrolizumab monotherapy. Additionally, the combination arm had a reduction in the risk of recurrence or death by 44%. Most reported treatment-related adverse events were grade 1/2, with the number of patient-reported treatment-related grade ≥3 adverse events being similar between the arms (25% vs 18%, respectively). Fatigue was the most common mRNA-4157-related grade 3 adverse event, and no mRNA-4157-related grade 4 or 5 adverse events were reported.

Eligible patients with completely resected, high-risk cutaneous melanoma were randomly assigned 2:1 to receive mRNA-4157 plus pembrolizumab or pembrolizumab as monotherapy. One milligram of mRNA-4157 was administered intramuscularly every 3 weeks for a total of 9 doses, and 200 mg of pembrolizumab was injected intravenously every 3 weeks for up to 18 cycles. The primary endpoint of KEYNOTE-942 was recurrence free survival in the overall intent-to-treat population. Safety was evaluated as a key secondary endpoint.

The study investigators concluded that “mRNA-4157 in combination with pembrolizumab as adjuvant therapy for resected high-risk melanoma significantly prolonged [recurrence free survival] compared to pembrolizumab without an increase in clinically meaningful adverse events. These results are the first to demonstrate improvement of [recurrence free survival] over adjuvant standard of care PD-1 blockade in resected high-risk melanoma and provide the first randomized evidence that a personalized neoantigen approach is potentially beneficial for cancer patients.”

Reference

1. Weber J. 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. Presented at the American Association for Cancer Research Annual Meeting 2023; April 14-19, 2023; Orlando, FL.