Melanoma coverage on Peptide News Digest is dominated by peptide cancer vaccine work. The most cited 2026 read: a randomized Phase I/II trial of a melanoma helper peptide vaccine combined with anti-CD27 antibody varlilumab reported 69% four-year disease-free survival in the combination arm versus 20% with vaccine alone — though varlilumab depleted circulating CD4+ T cells, raising questions about the mechanism.
Other threads: Evaxion's EVX-01 in melanoma, the Mel39 trial, and adjuvant immunotherapy work pairing peptide vaccines with checkpoint inhibitors. Several AACR 2026 abstracts also covered peptide-vaccine programs in melanoma.
Stories here cover trial readouts, AACR and ASCO presentations, and the broader peptide-vaccine field in melanoma. See #peptide-vaccine, #cancer-vaccine, and #mel39-trial.
Evaxion said on Friday, October 2, 2026 that it will present new immune data from its Phase 2 trial of EVX-01, a personalized, AI-designed peptide cancer vaccine given with Merck's Keytruda (pembrolizumab) to 16 patients with advanced melanoma, at the Society for Immunotherapy of Cancer meeting in Phoenix, with an oral presentation on November 6. Previously reported two-year results showed objective responses in 12 of 16 patients (75%), including four complete responses, and tumor-specific immune responses to 86% of the vaccine's neoantigen targets. Each patient receives a vaccine designed and manufactured from their own tumor's biology.
Merck (NYSE: MRK) and Moderna (NASDAQ: MRNA) announced Wednesday August 19, 2026 that the Phase 3 INTerpath-001 trial of intismeran autogene (V940 / mRNA-4157, an individualized neoantigen therapy) plus pembrolizumab (Keytruda) met its primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS) in adults with high-risk (Stage IIB-IV) resected cutaneous melanoma compared to Keytruda alone. Mechanism: intismeran autogene is a personalized mRNA therapy that encodes up to 34 tumor-specific neoantigen peptides selected from the individual patient's tumor mutation signature. The mRNA is delivered as a lipid nanoparticle injection; cells at the injection site translate the mRNA into the neoantigen peptides, which are then presented to the immune system to generate a targeted T-cell response against the patient's tumor. The Phase 3 readout is the first positive Phase 3 for an individualized neoantigen therapy and the first Phase 3 to demonstrate substantial improvement over Keytruda alone in the adjuvant melanoma setting. Trial design: randomized, double-blind, placebo- and active-comparator-controlled global Phase 3 evaluating safety and efficacy of the combination versus Keytruda alone. Phase 2b KEYNOTE-942 five-year follow-up data presented at the 2026 ASCO Annual Meeting had shown a 49% reduction in risk of recurrence or death and a 59% reduction in risk of distant metastasis or death for the combination versus Keytruda alone, and the Phase 3 readout confirms and extends those benefits. The result validates the personalized neoantigen mRNA vaccine platform and opens a substantial commercial pathway for the Merck-Moderna collaboration in adjuvant oncology settings beyond melanoma including non-small-cell lung cancer, renal cell carcinoma, and cutaneous squamous cell carcinoma where INTerpath studies are ongoing.
A post-hoc analysis in the International Journal of Cancer tracked 51 patients from the Mel39 randomized phase II trial of multipeptide vaccination for resected high-risk melanoma. At median follow-up of 16.1 years (21.2 years for surviving participants), the 12-peptide vaccine arm reported 65% 10-year and 49% 20-year overall survival vs. the 4-peptide arm (HR 0.64, 95% CI 0.29–1.40). The 20-year dataset represents among the longest published follow-up for any cancer peptide vaccine and reinforces that antigen breadth drives durability; sex-specific differences were documented, with females showing improved recurrence-free survival.
Evaxion's AI-designed personalized neoantigen peptide vaccine EVX-01 combined with Keytruda produced a 75% objective response rate at 2 years in advanced melanoma patients, with 86% of vaccine targets triggering de novo T-cell responses. Data were presented April 22 at AACR 2026; 3-year follow-up expected in H2 2026. The 86% target-hit rate demonstrates AI-designed peptide neoantigen selection maturing for cancer vaccines.
A randomized Phase I/II trial of a melanoma helper peptide vaccine with anti-CD27 antibody varlilumab reported 69% four-year disease-free survival in the combination arm versus 20% with vaccine alone. However, varlilumab depleted circulating CD4+ T cells, potentially limiting vaccine synergy and warranting further optimization.