mRNA-4157 (V940) personalized cancer vaccine — Drug Monograph

Brand names: V940

Drug class: Other

Mechanism of Action

Personalized mRNA neoantigen cancer vaccine encoding up to 34 patient-specific tumor neoantigens identified through next-generation sequencing of resected tumor and matched normal tissue, followed by bioinformatic neoantigen prediction and prioritization. The lipid nanoparticle-formulated mRNA is injected intramuscularly, taken up by antigen-presenting cells, and translated into neoantigen peptides that are presented on MHC class I and II molecules, priming neoantigen-specific cytotoxic CD8+ and helper CD4+ T-cell responses against the patient's unique tumor. Administered in combination with…

FDA Indications

• Adjuvant treatment of adults with resected stage IIB-IV melanoma in combination with pembrolizumab (FDA approved October 2023; KEYNOTE-942/mRNA-4157-P201 Phase 2b: 44% reduction in risk of recurrence or death [RFS HR 0.56] at ~2-year follow-up vs pembrolizumab monotherapy)

Common Side Effects

• Injection site reactions (pain, erythema, swelling — most common AE)
• Fatigue
• Flu-like symptoms (myalgia, chills, headache)
• Nausea
• Fever
• Arthralgia

Clinical Pearl

mRNA-4157/V940 represents the first FDA-approved personalized neoantigen cancer vaccine and validates the concept of individualized cancer immunotherapy. The ~8-week manufacturing window means patient selection and tumor biopsy must occur immediately after surgical resection. Each vaccine is unique to the patient's tumor mutational landscape — no two patients receive the same product. The benefit seen in KEYNOTE-942 (44% RFS improvement) may reflect synergy between PD-1 blockade (releasing…

Related Therapies & Mechanisms

• Lifileucel (Amtagvi) — Other · Melanoma
• Adagrasib (Krazati) — Other
• Arsenic Trioxide (Trisenox) — Other
• Asparaginase (L-asparaginase, E. coli) (Elspar) — Other