Vaccine Info

mRNA-4157 (V940) Individualized Neoantigen Therapy

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Last reviewed
April 7, 2024
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Robert Carlson, MD

mRNA-4157 (V940) Individualized Neoantigen Therapy

Moderna, Inc.'s mRNA-4157 (V940) is a personalized cancer vaccine (PCV). mRNA-4157 is a messenger RNA (mRNA)-based individualized neoantigen therapy (INT) consisting of a single synthetic mRNA coding for up to 34 neoantigens that is designed and produced based on the unique mutational signature of the DNA sequence of the patient's tumor. INTs are designed to train and activate an antitumor immune response by generating specific T-cell responses based on the unique mutational signature of a patient's tumor. Upon administration into the body, the algorithmically derived and RNA-encoded neoantigen sequences are endogenously translated and undergo natural cellular antigen processing and presentation, a critical step in adaptive immunity.

KEYTRUDA®, Merck's anti-PD-1 therapy, is an immunotherapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Based on clinical study results, combining mRNA-4157/V940 with KEYTRUDA may provide an additive benefit and enhance T cell-mediated destruction of tumor cells.

On November 10, 2020, Moderna issued interim data from the Phase 1 dose-expansion cohort study of mRNA-4157 combined with pembrolizumab. The data showed that mRNA-4157, combined with Keytruda, is well tolerated at all dose levels and produced responses measured by tumor shrinkage by RECIST 1.1 criteria in HPV(-) HNSCC patients. However, no responses were observed in MSS-CRC patients.

On December 13, 2022, mRNA-4157 (V940), in combination with KEYTRUDA, demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence or death compared to KEYTRUDA monotherapy in stage III/IV melanoma patients with a high risk of recurrence following complete resection. On January 9, 2023, the Company confirmed it plans to discuss the results with regulatory authorities, initiate a Phase 3 clinical study in melanoma patients in 2023, and rapidly expand to additional tumor types.

On February 22, 2023, Moderna and Merck announced that mRNA-4157/V940 was granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration (FDA) for the adjuvant treatment of patients with high-risk melanoma following complete resection. Moderna announced on April 16, 2023, that mRNA-4157 (V940), in combination with KEYTRUDA, reduced the risk of recurrence or death by 44% compared to KEYTRUDA alone in stage III/IV melanoma patients with a high risk of recurrence following complete resection. In addition, Moderna announced on June 5, 2023, distant metastasis-free survival (DMFS) results from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study.

On July 26, 2023, Merck and Moderna, Inc. announced initiating the pivotal Phase 3 randomized V940-001 clinical trial evaluating V940 (mRNA-4157). Merck and Moderna announced on December 11, 2023, the initiation of INTerpath-002, a pivotal Phase 3 randomized clinical trial evaluating V940 (mRNA-4157 in combination with KEYTRUDA as adjuvant treatment in patients with completely resected (R0) Stage II, IIIA or IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). Global recruitment of the INTerpath-002 has begun, and the first patients enrolled in Australia. On December 14, 2023, the companies announced follow-up data from the Phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study. In this planned analysis occurring with a median follow-up of approximately three years, adjuvant treatment with mRNA-4157 (V940) in combination with KEYTRUDA continued to demonstrate a clinically meaningful improvement in recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR=0.510 [95% CI, 0.288-0.906]; one-sided nominal p=0.0095) compared with KEYTRUDA alone. mRNA-4157 (V940) in combination with KEYTRUDA also continued to demonstrate a meaningful improvement in distant metastasis-free survival (DMFS), compared with KEYTRUDA alone, reducing the risk of developing distant metastasis or death by 62% (HR=0.384 [95% CI, 0.172-0.858]; one-sided nominal p= 0.0077).

Moderna's mRNA platform allows for investigational medicines that combine in a single mRNA therapy several different approaches to activate the immune system to attack cancer, either with mRNA encoding for common tumor proteins found across cancer types or multiple mRNAs encoding for various immunomodulatory proteins. In addition, personalized cancer vaccines are designed to prime the immune system so patients can generate a tailored antitumor response specific to their tumor mutation signature.

Moderna is headquartered in Cambridge, Mass. To learn more, visit

mRNA-4157 (V940) Indication

mRNA-4157 is indicated to vaccinate patients with metastatic common epithelial cancers (melanoma). It is an mRNA-based individualized, therapeutic personalized cancer vaccine targeting 20 tumor-associated antigens expressed explicitly by the patient's cancer cells, with potential immunostimulatory and antineoplastic activities. And as adjuvant treatment in patients with completely resected (R0) Stage II, IIIA, or IIIB (with nodal involvement [N2]) NSCLC. 

mRNA-4157 (V940) Dosage

In a phase 2 study, patients are vaccinated intramuscularly at 2-week intervals for (4) cycles, and dosing may be repeated for the second vaccination course.

mRNA-4157 (V940) News

January 2024 - The Lancet published results from a phase 2b study - Interpretation - Adjuvant mRNA-4157 plus pembrolizumab prolonged recurrence-free survival versus pembrolizumab monotherapy in patients with resected high-risk melanoma and showed a manageable safety profile.

December 14, 2023 - Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, commented in a press release, "We are pleased to see the results from this planned analyses on recurrence-free survival for V940 (mRNA-4157), and look forward to working with Moderna in expanding our clinical development program for the individualized neoantigen therapy."

December 11, 2023 - "As lung cancer is the leading cause of cancer death worldwide, there is a need for continued scientific advancements to help fight this disease at earlier stages when patients have the best chance for better outcomes," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories.

July 26, 2023 - "As we continue our efforts to advance novel treatment options for patients with high-risk Stage IIB-IV melanoma, the initiation of the V940-001 Phase 3 trial represents an important step forward in these efforts and our study of individualized neoantigen therapy," said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories.

April 16, 2023 - "Data from KEYNOTE-942 provide evidence for the potential of mRNA-4157 (V940) in combination with KEYTRUDA to improve recurrence-free survival when given to patients with resected high-risk melanoma," said Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer, Merck Research Laboratories.

February 22, 2023 - Stephen Hoge, M.D., Moderna's President, said in a press release, "mRNA-4157/V940 in combination with KEYTRUDA provided the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and potentially represents a new frontier in treating melanoma and other cancers."

June 1, 2019 - The data showed that the mRNA personalized cancer vaccine mRNA-4157, given alone or combined with Merck's pembrolizumab (KEYTRUDA®), was well-tolerated at all doses tested and elicited neoantigen-specific T-cell responses. No vaccine-related serious adverse events were reported for the PCV when administered to patients as a monotherapy or combined with pembrolizumab.

December 13, 2016 - Moderna announced 'We are developing an mRNA-based personalized cancer vaccine with the potential to prime the immune system to recognize cancer cells and mount a strong, tailored response to each patient's cancer."

mRNA-4157/V940 Clinical Trials

Clinical Trial NCT03313778: Safety, Tolerability, and Immunogenicity of mRNA-4157 Alone in Subjects With Resected Solid Tumors and Combination With Pembrolizumab in Subjects With Unresectable Solid Tumors (KEYNOTE-603Thishis phase 1 studies is to assess the safety, tolerability, and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and combination with pembrolizumab in subjects with unresectable solid tumors. 

Clinical Trial NCT03897881: An Efficacy Phase 2 Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Patients With High-Risk Melanoma (KEYNOTE-942). The purpose of this Phase 2 study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence-free survival (RFS) compared to pembrolizumab alone in patients with complete resection of cutaneous melanoma and a high-risk of recurrence.

The results of this ongoing study were announced on December 13, 2022. More information about this study and its results can be found here.

Clinical Trials

No clinical trials found