mRNA-4157/V940
InvestigationalA 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.
V940 · mRNA-4157 · INTerpath vaccine
24 human studies
- Preclinical
- 14%
- Clinical
- 86%
Based on 28 cited sources
clinically demonstrated · moderate confidence
Demonstrated effect magnitude — not a recommendation or safety claim.
Research Depth 64: single adequately-powered open-label Phase 2b RCT KEYNOTE-942 (38246194, n=157, HR 0.561 for RFS, primary p=0.053) plus Phase 1 KEYNOTE-603 (39115419) — 1A=28 (single RCT n>=50, not yet >=2 independent RCTs as Phase 3 INTerpath has no results); 1B=10 (open-label, "some concerns" RoB); 1C=6 (total human N ~190-200, 50-300 band); 1D=13 (direct resected-melanoma population/IM route/RFS-DMFS outcomes); 1E=7 (substantial neoantigen-vaccine preclinical + early-phase program). Mechanism 74: 2A=30 (neoantigen/MHC target with functional T-cell confirmation, 39115419), 2B=26 (LNP->APC->translation->MHC->CD8/CD4 chain mapped), 2C=8 (fixed 1mg dose, limited formal dose-response), 2D=10 (in-vivo mammalian + human confirmation). Plausibility 89: 3A=34 (full mechanism->T-cell surrogate->RFS/DMFS chain each supported), 3B=24 (coherent with checkpoint/tumor immunology), 3C=18 (class analogues: autogene cevumeran, BioNTech mutanome 28678784), 3D=13 (tightly scoped adjuvant-melanoma claim). Global Coverage 44: 4A=14 (mRNA-4157 findings within one Moderna/Merck sponsor cluster though the neoantigen-vaccine class is independently replicated, 28678778/28678784), 4B=12 (USA+Australia sites), 4C=13 (modest compound-specific literature, broad class context, 25765070 supports neoantigen-burden rationale), 4D=5 (FDA Breakthrough Therapy + Phase 3 registration, investigational not approved). Community Experience 10: trials-only product with negligible documented real-world use (5A=3, 5B=3, 5C=0, 5D=4). Effectiveness basis clinical (moderate): KEYNOTE-942 18-month RFS 79% vs 62% (HR 0.561), DMFS improved — moderate- large effect on patient-relevant outcomes, head-to-head superior to pembrolizumab monotherapy but Phase 2b primary endpoint borderline (p=0.053) and Phase 3 confirmation pending.
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:
Patient tumor DNA is sequenced to identify up to 34 unique neoantigens (mutated proteins) that distinguish cancer cells from normal cells.
Personalized mRNA encoding all neoantigens is encapsulated in lipid nanoparticles and injected, where it enters antigen-presenting cells.
Cells express neoantigens on MHC molecules, activating CD8+ killer T cells and CD4+ helper T cells specific to the patient’s tumor.
Combined with pembrolizumab (PD-1 inhibitor) to release immune brakes, allowing activated T cells to attack residual cancer cells at full capacity.
Key Research: Weber JS et al. (Lancet, 2024) demonstrated 44% reduction in recurrence or death with combination therapy. PMID:38246194
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
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.
PMID:38246194Subsequent 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.
PMID:38246194mRNA-4157 dosing completes at approximately 6 months. Pembrolizumab continues for total of 18 doses (~1 year). Ongoing immune surveillance targets residual micrometastatic disease.
PMID:38246194Follow-up in KEYNOTE-942 demonstrated an approximately 44% reduction in recurrence risk (hazard ratio 0.561). Distant metastasis-free survival improved. Overall survival trend favorable but data still maturing.
PMID:38246194Research-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.
Good Signs (6 indicators)
Warning Signs (5 indicators)
Bad Signs (5 indicators)
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.
Pembrolizumab
SynergisticDesigned 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
CompatibleAnother PD-1 inhibitor. Theoretical compatibility based on similar mechanism to pembrolizumab, but no clinical data exists for this combination.
Ipilimumab
CompatibleCTLA-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.
Key Studies Cited
Full reference list available on request. All citations link to PubMed for verification.
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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