Investigational — This vaccine is not yet approved for general use. Information is for educational purposes only. Participation in clinical trials requires enrolment at an authorised trial centre.
mRNA-4157 / V940
Also known as: Individualized Neoantigen Therapy · INT · mRNA cancer vaccine + pembrolizumab
mRNA-4157 is the most advanced personalised cancer vaccine in the world. Each dose is bespoke: after surgical tumour removal, the tumour's DNA is sequenced, and an algorithm identifies up to 34 unique mutations (neoantigens) present on the patient's cancer cells but not on healthy cells. An mRNA vaccine encoding those 34 neoantigens is then synthesised and manufactured in approximately 6 weeks, then given with pembrolizumab (Keytruda). The Phase 2b KEYNOTE-942 trial in high-risk melanoma showed a stunning 44% reduction in recurrence or death versus pembrolizumab alone — the most significant advance in adjuvant melanoma therapy in years. Phase 3 trials are now underway across multiple cancer types.
What It Targets
Target Antigen
Patient-specific tumour neoantigens (personalised per tumour mutation profile)
Cancers Targeted
How It Works
Tumour biopsy DNA is sequenced → an AI algorithm (NetMHCpan) predicts which mutations generate peptides that bind to the patient's specific HLA molecules (the individual's immune recognition system) → up to 34 of the best neoantigen-encoding mRNA sequences are synthesised into a single vaccine → the mRNA is encapsulated in lipid nanoparticles (the same technology as COVID mRNA vaccines) → injected subcutaneously, dendritic cells take up the mRNA and present the neoantigens on MHC-I and MHC-II → tumour-specific CD8+ killer T cells and CD4+ helper T cells are primed to recognise and kill remaining cancer cells bearing those mutations. Pembrolizumab (anti-PD-1) prevents T-cell exhaustion and amplifies the response.
Key Trial Results
- KEYNOTE-942 Phase 2b (melanoma): 44% reduction in recurrence or death vs pembrolizumab alone (HR 0.56, p=0.0266)
- 2-year recurrence-free survival: 78.6% (vaccine+pembro) vs 62.2% (pembro alone)
- Distant metastasis or death: 65% reduction in the combination arm
- Response seen even in patients with low tumour mutational burden — broader than checkpoint inhibitors alone
- Phase 3 V940-001 (adjuvant melanoma) enrolled globally — results expected 2026
- Phase 2 expansions in NSCLC, bladder, colorectal, and renal cell carcinoma announced 2023–2024
- EU: EMA granted PRIME designation (accelerated review for promising therapies)
Regulatory Status & Availability
Approval Status
Breakthrough Therapy Designation (FDA, 2023). Phase 3 KEYNOTE-942 / V940-001 ongoing.
Estimated Availability
Potentially 2026–2027 if Phase 3 succeeds; FDA Breakthrough pathway
Important Considerations
- Manufacturing takes ~6 weeks post-surgery — timing is critical; tumour must be fully resected
- Cost will likely be extremely high; access and insurance coverage unresolved
- Currently adjuvant (post-surgery) setting only — not designed for active metastatic disease
- Neoantigen selection depends on adequate tumour tissue and successful sequencing — not all tumours yield sufficient material
- Pembrolizumab carries its own immune-related adverse event (irAE) risks (colitis, pneumonitis, thyroiditis)
- Phase 3 results not yet in — current data from Phase 2b only (n=157)
Research References
iOnco provides this information for educational purposes only. Cancer vaccine availability, trial eligibility, and access pathways change frequently. Always discuss vaccination decisions and clinical trial participation with your oncologist or healthcare provider.