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ID: MRNA-4157/V940 STATUS: ACTIVE

mRNA-4157/V940

Investigational

Also known as: V940, mRNA-4157, INTerpath vaccine

A personalized mRNA cancer vaccine encoding up to 34 patient-specific neoantigens, developed jointly by Moderna and Merck. Designed for use in combination with pembrolizumab (Keytruda) for adjuvant treatment of resected high-risk melanoma and other solid tumors. Phase 2b KEYNOTE-942 demonstrated 44-50% reduction in recurrence or death. FDA Breakthrough Therapy designation granted. Multiple Phase 3 trials (INTerpath) ongoing.

Other High Evidence 28 Sources

Research Statistics

Total Sources
28
Human Studies
24
Preclinical
4
Evidence Rating High Evidence
Research Depth 4/5
Global Coverage 4/5
Mechanism Plausibility 4/5
Overall Score
4 /5

Moderna personalized neoantigen mRNA cancer vaccine with FDA Breakthrough Therapy designation; KEYNOTE-942 Phase 2b data and INTerpath Phase 3 trials demonstrate substantial multinational evidence base.

Last reviewed February 2026 How we rate →
✓
Evidence Level
high
Not approved for human use by any regulatory agency
Limited human clinical trial data
Consult a healthcare provider before use
Not FDA Approved WADA Prohibited

Research Dossier

01 / 7
01 Overview 02 Mechanism 03 Evidence 04 What to Expect 05 Quality 06 Interactions 07 References

Overview

What is mRNA-4157/V940 and what does the research say?

Identity
Also Known As
V940 • mRNA-4157 • INTerpath vaccine
Type
Lipid nanoparticle-encapsulated mRNA
Length
0 amino acids
Weight
N/A (mRNA therapeutic)
Sequence
N/A (mRNA therapeutic)
Molecular Structure
Hydrophobic
Polar
Positive
Negative

Mechanism of Action

The mechanism of mRNA-4157 is based on personalized neoantigen presentation through lipid nanoparticle-encapsulated mRNA delivery, validated in Phase 2b clinical trials.

How It Works (Simplified)

mRNA-4157 functions as a personalized cancer vaccine that trains the immune system to recognize and attack tumor-specific neoantigens:

1
Tumor Sequencing

Patient tumor DNA is sequenced to identify up to 34 unique neoantigens (mutated proteins) that distinguish cancer cells from normal cells.

2
mRNA Delivery

Personalized mRNA encoding all neoantigens is encapsulated in lipid nanoparticles and injected, where it enters antigen-presenting cells.

3
T Cell Activation

Cells express neoantigens on MHC molecules, activating CD8+ killer T cells and CD4+ helper T cells specific to the patient’s tumor.

4
Checkpoint Synergy

Combined with pembrolizumab (PD-1 inhibitor) to release immune brakes, allowing activated T cells to attack residual cancer cells at full capacity.

Scientific Pathways

LNP-mRNA Antigen Presentation Pathway (Immune Priming)

mRNA-4157 (IM injection) → LNP uptake by APCs → Cytoplasmic mRNA translation
                                                          ↓
                                              Neoantigen protein production
                                                          ↓
                                              Proteasomal processing → MHC I/II presentation
                                                          ↓
                                              CD8+ and CD4+ T cell activation

Combination Immunotherapy Pathway (Synergistic Anti-Tumor Response)

mRNA-4157: Neoantigen targeting → T cells recognize tumor-specific mutations
                                              +
Pembrolizumab: PD-1 blockade → T cell exhaustion prevented
                                              ↓
                                  Enhanced tumor cell killing

Key Research: Weber JS et al. (Lancet, 2024) demonstrated 44% reduction in recurrence or death with combination therapy. PMID:38029730

Important Limitations

  • Investigational product; not approved for any indication
  • Phase 3 confirmatory trials (INTerpath) ongoing with results expected 2027-2029
  • Requires approximately 6 weeks manufacturing time from tumor biopsy
  • Available only through registered clinical trials
  • Long-term efficacy and overall survival benefit not yet confirmed

Evidence-Chained Benefits

Evidence-Chained Benefits

Research findings linked to mechanisms and clinical outcomes

Mechanism LNP-mRNA delivery to antigen-presenting cells, enabling neoantigen expression and MHC presentation
Established 12 direct studies
Benefit shown to induce neoantigen-specific T cell responses
Evidence Level
High
8 Human
4 Animal
6 In Vitro
Mechanism CD8+ cytotoxic T cell activation against patient-specific tumor neoantigens
Established 8 direct studies
Benefit shown to reduce cancer recurrence in resected melanoma
Evidence Level
High
6 Human
2 Animal
4 In Vitro
Mechanism Synergistic immune activation through combined antigen presentation and checkpoint blockade
Established 6 direct studies
Benefit shown to enhance anti-tumor immunity when combined with pembrolizumab
Evidence Level
High
4 Human
2 Animal
3 In Vitro
Mechanism Confidence
Established
Supported
Emerging
Evidence Level
High
Moderate
Low
Very Low

What to Expect

Timeline based on observations from published studies. Individual responses may vary.

Week 1-3 PMID:38029730

First dose administered intramuscularly. Injection site reactions and transient systemic symptoms (fatigue, fever, myalgia) commonly observed. LNP-mRNA uptake by antigen-presenting cells initiates immune priming.

Week 3-18 PMID:38029730

Subsequent doses given every 3 weeks (9 total doses over ~6 months). T cell responses develop and expand against patient-specific neoantigens. Concurrent pembrolizumab given every 3 weeks.

Month 6-12 PMID:38029730

mRNA-4157 dosing completes at approximately 6 months. Pembrolizumab continues for total of 18 doses (~1 year). Ongoing immune surveillance targets residual micrometastatic disease.

Year 1-3 PMID:38029730

Long-term follow-up in KEYNOTE-942 demonstrated sustained 44-50% reduction in recurrence risk. Distant metastasis-free survival improved. Overall survival trend favorable but data still maturing.

Research-Based Observations

This timeline reflects observations from published clinical and preclinical studies. Individual responses may vary significantly. This is not a guarantee of effects or a dosing schedule. Consult qualified healthcare providers for personalized guidance.

Quality Checklist

Visual indicators to help evaluate mRNA-4157/V940 product quality

Good Signs (6 indicators)
Administered only in approved clinical trial settings
Personalized manufacturing from patient tumor sequencing
Approximately 6 weeks from biopsy to individualized product
GMP manufacturing at Moderna facilities
Lipid nanoparticle formulation for mRNA stability
Up to 34 neoantigens encoded per individual vaccine
Warning Signs (5 indicators)
Not available outside of clinical trials
Requires tumor resection and adequate tissue for sequencing
Manufacturing timeline may delay treatment initiation
Patient must be eligible for pembrolizumab combination
Requires adequate HLA typing for neoantigen prediction
Bad Signs (5 indicators)
Any product offered outside registered clinical trials is fraudulent
No generic or biosimilar versions exist
Online sales claiming mRNA-4157 availability are scams
Product cannot be compounded or replicated at pharmacy level
Patient-specific; cannot be transferred between individuals
Positive quality indicator
Requires evaluation
Potential quality issue

For Research Evaluation Only

These quality indicators are general guidelines based on typical peptide characteristics. Professional laboratory testing (HPLC, mass spectrometry) provides definitive quality verification. This checklist is for initial visual evaluation only.

Peptide Interactions

Known and theoretical interactions when combining mRNA-4157/V940 with other peptides. Based on published research and mechanistic considerations.

Synergistic
Compatible
Caution
Avoid

Pembrolizumab

Synergistic
Synergistic

Designed as combination therapy. mRNA-4157 provides neoantigen targets while pembrolizumab removes PD-1 immune checkpoint inhibition. KEYNOTE-942 demonstrated 44% risk reduction with combination vs pembrolizumab alone.

Nivolumab

Compatible
Compatible

Another PD-1 inhibitor. Theoretical compatibility based on similar mechanism to pembrolizumab, but no clinical data exists for this combination.

Ipilimumab

Compatible
Compatible

CTLA-4 checkpoint inhibitor with complementary mechanism. Triple combination (mRNA-4157 + PD-1 + CTLA-4) not yet studied clinically.

Research Note: Interaction data is based on published literature, mechanistic understanding, and theoretical considerations. Most peptide combinations lack direct clinical study. This information is for educational purposes only and does not constitute medical advice. Always consult qualified healthcare providers.

References

28 Sources
24 Human
4 Preclinical

Key Studies Cited

RCT Weber JS et al. 2024
PMID:38029730
Human Patel MR et al. 2022
PMID:35489362
Human Ott PA et al. 2017
PMID:28678784

Full reference list available on request. All citations link to PubMed for verification.

Methodology Note

This dossier synthesizes available evidence from peer-reviewed literature, regulatory documents, and clinical trial registries. Evidence strength ratings follow a modified GRADE approach.

For complete methodology details, see our Methodology page.

Important Disclaimer

This dossier is for educational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before making health decisions.

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