Individualized neoantigen therapy mRNA-4157 (V940) plus pembrolizumab in resected melanoma: 3-year update from the mRNA-4157-P201 (KEYNOTE-942) trial.

• DOI: 10.1200/jco.2024.42.17_suppl.lba9512
• Publication Date: 2024-06-05T13:28:57Z
• Authors: Jeffrey S. Weber; Muhammad Adnan Kh...; Matteo S. Carlino; Tarek Meniawy; Matthew H. Taylor; George Ansstas; Kevin B. Kim; Meredith McKean; Ryan J. Sullivan; Mark B Faries; Thuy Tran; Charles Lance Cowey; Theresa Medina; Jennifer Margaret...; Victoria Atkinson; Geoffrey Thomas G...; Jason J. Luke; Elizabeth Iannott...; Georgina V. Long; Robert S. Meehan
• Keywords: Clinical endpoint

LBA9512 Background: mRNA-4157 is a novel, mRNA-based individualized neoantigen therapy designed to increase endogenous antitumor T-cell responses by targeting unique patient (pt) tumor mutations. In the primary analysis of Ph 2 mRNA-4157-P201 (KEYNOTE-942) trial (median planned follow-up, 23 mo), pts with completely resected high-risk stage IIIB–IV cutaneous melanoma receiving + pembrolizumab (pembro; combo) had prolonged recurrence-free survival (RFS) and distant metastasis-free (DMFS) vs pembro alone (Weber JS, et al. Lancet. 2024). Methods: Pts were assigned 2:1 (1 mg IM, max 9 doses) (200 IV, 18 cycles) or alone. The endpoint was investigator-assessed RFS; secondary endpoints DMFS safety. This supportive triggered when last randomized pt ≥2 y follow-up. Translational subgroup analyses also reported. HLA genotypes analyzed exome sequencing DNA from PBMC. RFS not formally tested; nominal 2-sided p-values are descriptive. Results: With an additional year follow-up (data cutoff, 03 Nov 2023; median [range], 34.9 [25.1–51.0] mo) after analysis, minimal new events occurred. benefit in combo arm maintained 49% risk reduction recurrence and/or death (HR [95% CI], 0.510 [0.288–0.906]; p-value 0.019). 2.5-yr rate treatment (tx) 74.8% 55.6%. Combo tx produced clinically meaningful, sustained improvement 0.384 [0.172–0.858], 0.0154). OS favored alone; 2.5-y 96.0% 90.2% 0.425 [0.114–1.584]). TMB high 0.564 [0.253–1.258]), non-high (0.571 [0.245–1.331]), PD-L1 positive (0.471 [0.226–0.979]), negative (0.147 [0.034–0.630]), ctDNA (0.207 [0.091–0.470]) subgroups; HR estimable. No significant associations between individual alleles observed either arm. Maximal heterozygosity at class I genotype loci (A, B, C) improved homozygosity for ≥1 locus [0.179–1.01]) but (1.252 [0.498–3.146]). well tolerated safety profile consistent previous no potentiation immune-related AEs. Conclusions: current ∼3 showed durable meaningful long-term A trend observed. translational results suggest may broader population Clinical information: NCT03897881 .