Intismeran Autogene mRNA Vaccine Phase III — PatSnap Eureka
Intismeran Autogene mRNA Cancer Vaccine: Phase III Adjuvant Melanoma Readout
mRNA-4157/V940 (intismeran autogene) combined with pembrolizumab (Keytruda) delivered a 44% reduction in risk of recurrence or death at 3-year follow-up in high-risk resected melanoma. Explore the patent landscape, clinical data, and IP strategy powering this landmark program.
KEYNOTE-942: Durable Survival Benefit Across 3-Year Follow-Up
The KEYNOTE-942 Phase 2b trial evaluated mRNA-4157 (V940) — now designated intismeran autogene — in combination with pembrolizumab versus pembrolizumab alone in patients with high-risk resected melanoma (Stage IIB–IV). Updated data from Luke et al. (2024) confirmed a 3-year recurrence-free survival (RFS) rate of 74.8% in the combination arm versus 55.6% in the comparator arm, representing a 44% reduction in risk of recurrence or death.
A distant metastasis-free survival (DMFS) benefit was also observed in the combination arm, further supporting the clinical meaningfulness of the signal. The safety profile remained manageable with no new safety signals identified at extended follow-up, consistent with the established profiles of each agent administered as monotherapy. These results provided the pivotal rationale for advancement to the Phase 3 program.
Immune correlate analyses confirmed that neoantigen-specific CD8+ T cell responses were induced by the vaccine, providing mechanistic validation of the platform's mode of action in the clinical setting. This evidence base supports the ongoing patent landscape analysis and IP strategy monitoring available through PatSnap Eureka.
How mRNA-4157 + Pembrolizumab Generates Synergistic Anti-Tumour Immunity
The combination exploits complementary immune pathways — vaccine-driven T-cell priming and checkpoint-driven T-cell rescue — to produce durable anti-tumour responses neither agent achieves alone.
Personalised Neoantigen mRNA Encoding
Whole exome sequencing and RNA sequencing of the patient's tumour identify somatic mutations. Machine learning algorithms select up to 34 high-quality mutation-associated neoantigens (MANAs). These are encoded as a single mRNA construct, formulated in lipid nanoparticles (LNPs) for intramuscular delivery, and manufactured within weeks of biopsy.
Up to 34 neoantigens per constructDendritic Cell Cross-Presentation & T-Cell Activation
LNP-delivered mRNA is taken up by antigen-presenting cells, particularly dendritic cells, which cross-present neoantigen peptides to both CD4+ helper T cells and CD8+ cytotoxic T cells. This generates a de novo, patient-specific anti-tumour immune response targeting mutations unique to that patient's cancer.
CD4+ and CD8+ T cell inductionPembrolizumab Reverses T-Cell Exhaustion
Tumour-infiltrating T cells upregulate PD-1, rendering them exhausted and unable to kill cancer cells. Pembrolizumab (anti-PD-1) blocks this suppressive signal, restoring effector function. In combination with the vaccine, pembrolizumab sustains the newly primed neoantigen-specific T cells, preventing their exhaustion in the tumour microenvironment.
PD-1 blockade synergyImmune Memory and Recurrence Prevention
The combination of vaccine-induced T-cell priming and checkpoint-maintained effector function produces immune memory against patient-specific neoantigens. Clinical evidence from KEYNOTE-942 confirms that neoantigen-specific CD8+ T cell responses are detectable and durable, correlating with the sustained recurrence-free survival benefit observed at 3-year follow-up.
Durable immune memory confirmedIP Filing Activity and Clinical Outcome Data: mRNA-4157 Programme
PatSnap Eureka analysis of ModernaTX patent filings and published clinical data from the KEYNOTE-942 programme.
ModernaTX Patent Portfolio by Technology Domain
Distribution of identified ModernaTX patents across five core technology domains in the personalised mRNA cancer vaccine programme, based on PatSnap Eureka analysis.
3-Year RFS Rate Comparison: Combination vs Monotherapy
KEYNOTE-942 Phase 2b: mRNA-4157 + pembrolizumab (74.8% RFS) vs pembrolizumab alone (55.6% RFS) at 3-year follow-up in high-risk resected melanoma Stage IIB–IV.
ModernaTX Core Patent Portfolio: mRNA-4157/V940 Programme
PatSnap Eureka identified 20+ ModernaTX patents covering the full personalised mRNA cancer vaccine value chain, from neoantigen epitope selection to manufacturing and clinical combination regimens. BioNTech SE holds competing IP in individualized mRNA cancer vaccines with LNP delivery and checkpoint inhibitor combinations.
Monitor Competitive IP in Real Time
Track new filings from Moderna, BioNTech, and emerging players across the personalised mRNA vaccine space with PatSnap Eureka alerts.
Predictive Biomarkers and Pipeline Expansion Beyond Melanoma
KEYNOTE-942 biomarker analyses and the mRNA-4157 pipeline expansion to NSCLC and other solid tumours represent the next strategic frontier for the Moderna/Merck collaboration.
Tumour Mutational Burden as a Predictive Biomarker
Biomarker analyses from the KEYNOTE-942 cohort identified tumour mutational burden (TMB), neoantigen quality, and immune gene expression signatures as predictive of recurrence-free survival benefit. High TMB and CD8+ T-cell infiltration were associated with superior outcomes, supporting patient selection strategies for Phase 3 enrollment.
Neoantigen Quality and Immune Gene Expression Signatures
Beyond TMB, neoantigen quality metrics — including predicted MHC binding affinity and expression levels — and immune gene expression signatures were identified as independent predictors of RFS benefit. These biomarker correlates are now incorporated into the patient selection strategy for the Phase 3 programme and are covered in ModernaTX patent WO2024054836A1.
AI-Powered Intelligence for mRNA Cancer Vaccine R&D and IP Strategy
PatSnap Eureka brings together patent data, clinical literature, and AI-driven analysis to give oncology R&D teams and IP professionals a complete picture of the personalised mRNA vaccine landscape. Whether you are tracking the mRNA-4157/V940 programme, monitoring BioNTech's competing filings, or assessing freedom-to-operate for a new neoantigen selection algorithm, Eureka provides the intelligence you need.
The PatSnap Analytics platform enables patent landscape analysis across the full mRNA oncology space, including LNP delivery systems, neoantigen prediction algorithms, and combination immunotherapy regimens. Integrated literature search surfaces clinical evidence from sources including NEJM, ASCO, and ESMO alongside patent data.
For life sciences teams, PatSnap's life sciences solution provides dedicated workflows for drug target validation, competitive intelligence, and clinical trial monitoring — all accessible from a single platform. The PatSnap API enables integration of patent intelligence directly into R&D workflows and data pipelines.
Intismeran Autogene mRNA Vaccine — Key Questions Answered
Intismeran autogene (also known as mRNA-4157 or V940) is a personalized mRNA cancer vaccine developed by Moderna. It encodes up to 34 patient-specific tumor neoantigens identified through whole exome and RNA sequencing, formulated in lipid nanoparticles for intramuscular administration. It is being evaluated in combination with pembrolizumab (Keytruda) in the adjuvant melanoma setting.
Updated KEYNOTE-942 data with extended follow-up showed that mRNA-4157 (V940) plus pembrolizumab demonstrated a 44% reduction in risk of recurrence or death at 3-year follow-up compared to pembrolizumab alone in high-risk resected melanoma (Stage IIB-IV). The 3-year recurrence-free survival rate was 74.8% in the combination arm versus 55.6% in the comparator arm. A distant metastasis-free survival benefit was also observed, with a manageable safety profile.
The combination works through complementary immune mechanisms. The personalized mRNA vaccine primes neoantigen-specific CD4+ and CD8+ T cells via dendritic cell cross-presentation, generating a de novo anti-tumor immune response. Pembrolizumab, an anti-PD-1 checkpoint inhibitor, reverses T-cell exhaustion and sustains the activated T-cell response. Together, they produce synergistic anti-tumor immunity that neither agent achieves alone.
Biomarker analyses from the KEYNOTE-942 cohort identified tumor mutational burden (TMB), neoantigen quality, and immune gene expression signatures as predictive of recurrence-free survival benefit. High TMB and CD8+ T-cell infiltration were associated with superior outcomes, supporting patient selection strategies for Phase 3 enrollment.
ModernaTX holds a broad and deep patent portfolio covering personalized cancer vaccine epitope selection using machine learning algorithms, LNP formulation and delivery, adjuvant regimens in the post-surgical setting, combination use with anti-PD-1 antibodies including pembrolizumab, manufacturing processes for rapid vaccine production, and methods for predicting patient response. Key patents include WO2022261018A1, WO2024054834A1, and US20240207407A1, among others. BioNTech SE holds competing IP in individualized mRNA cancer vaccines with LNP delivery and checkpoint inhibitor combinations.
Yes. The mRNA-4157 (V940) program is being expanded from melanoma to non-small cell lung cancer (NSCLC) and other solid tumors. Phase 3 trials are underway for melanoma and NSCLC. The LNP formulation, neoantigen selection algorithms, and checkpoint inhibitor combination rationale developed in melanoma are being translated to these additional indications.
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References
- Luke JJ et al. "Adjuvant Pembrolizumab Plus Personalized mRNA Cancer Vaccine in High-Risk Resected Melanoma: Updated Results from KEYNOTE-942." 2024.
- Weber JS et al. "Personalized mRNA Cancer Vaccine in Combination with Pembrolizumab Provides Durable Benefit in Resected High-Risk Melanoma." 2024.
- Sullivan RJ et al. "mRNA-4157 (V940) Individualized Neoantigen Therapy: Clinical Evidence and Future Development in Melanoma." 2024.
- Snyder A et al. "Neoantigen Cancer Vaccines: Mechanisms, Clinical Development and Future Directions." 2024.
- Milhem M et al. "Biomarkers Predictive of Response to Personalized mRNA Cancer Vaccine in Melanoma." 2023.
- de Azambuja E et al. "Combination of Personalized Neoantigen mRNA Vaccine and Checkpoint Inhibitor in Solid Tumors: A Systematic Review." 2024.
- Sahin U et al. "Personalized Cancer Vaccines: Current State and Future Directions." 2023.
- Besse B et al. "mRNA Cancer Vaccines in Non-Small Cell Lung Cancer: Translation of Melanoma Findings." 2024.
- Balachandran VP et al. "Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer." The Lancet. 2023.
- ModernaTX, Inc. Patent WO2022261018A1: "Combination Cancer Vaccine and Anti-PD-1 Therapy for Melanoma." 2022.
- ModernaTX, Inc. Patent WO2024054834A1: "mRNA Cancer Vaccine Combination with Anti-PD-1 for Melanoma." 2024.
- ModernaTX, Inc. Patent US20240207407A1: "Personalized Cancer Vaccine Epitope Selection." 2024.
- National Cancer Institute (NCI). Tumour Mutational Burden in Cancer Research.
- New England Journal of Medicine. Oncology Clinical Trial Publications.
- The Lancet. Cancer Immunotherapy Research.
All data and statistics on this page are sourced from the references above and from PatSnap's proprietary innovation intelligence platform.
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