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The world’s first neoantigen mRNA vaccine for personalized tumors
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Starting phase 3 clinical trial: The world’s first neoantigen mRNA vaccine for personalized tumors.
On July 26, Merck and Moderna announced the initiation of a pivotal Phase 3 clinical trial (V940-001) of tumor neoantigen mRNA vaccine (mRNA-4157) + Keytruda in combination with adjuvant therapy for operable stage IIB-IV high-risk melanoma . Currently, the trial has started global patient recruitment, and the first patients are being enrolled in Australia.
The V940-001 trial is a randomized, double-blind, placebo- and active-referenced control design, and plans to enroll approximately 1,089 melanoma patients in more than 25 countries and more than 165 centers .
The primary endpoint of the trial is recurrence-free survival (RFS), and secondary endpoints include distant metastasis-free survival, overall survival (OS) and safety.
In addition, a query of information about the V940-001 trial registered on clinicaltrials.gov shows that the study is expected to be completed by October 2029 .
Figure 1: V940-001 Trial Registration Information (Source: ClinicalTrials.gov)
mRNA-4157 is a personalized tumor neoantigen vaccine developed for the unique tumor mutations of each cancer patient . It contains a single synthetic mRNA molecule encoding up to 34 neoantigens .
T cells respond to stimulate an immune response.
In February 2023 , the vaccine was certified as a breakthrough therapy by the FDA ; in April, it was also qualified as a Priority Medicine (PRIME) by the EMA , and became the world’s first mRNA tumor vaccine to receive this certification.
In June 2016, Merck invested US$200 million in down payment to invest in Moderna to develop mRNA-4157. Up to now, mRNA-4157 combined with K drug has shown excellent tumor therapeutic potential :
- In 2019 , Moderna reported positive results. Out of 20 patients with solid tumors who received at least one dose of mRNA-4157 (0.04-1.0mg) and drug K, 6 achieved objective remission.
- In 2020, the HPV-head and neck squamous cell carcinoma subgroup of the KEYNOTE-603 study also made positive progress. Among the 10 patients receiving combination therapy, 5 patients achieved objective remission, and the PFS reached 9.8 months, which was better than that of the previous K drug monotherapy group (14.6% objective remission, PFS only 2.0 months).
- In 2022, Merck announced that the phase IIb study (KEYNOTE-942) of mRNA-4157 combined with K drug adjuvant treatment of completely resected stage III/IV melanoma reached the primary endpoint of RFS, which can significantly reduce the risk of recurrence or death by 44%.
- In 2023, Merck and Moderna announced the efficacy and safety of the combination of mRNA-4157 and Keytruda in 157 patients with surgically resected high-risk melanoma (stage III/IV) at the ASCO annual meeting. In the total intent-to-treat (ITT) population, adjuvant treatment with mRNA-4157 in combination with Keytruda demonstrated a statistically significant and clinically meaningful improvement in the secondary endpoint of distant metastasis-free survival (DMFS) compared to Keytruda alone The risk of distant metastasis or death was reduced by 65% (HR=0.347, 95% CI: 0.145-0.828]; one-sided P value=0.0063).
Personalized neoantigen vaccines can bring significant clinical benefits to cancer patients, but this type of vaccine still faces many challenges—the development of a stable, safe therapeutic strategy that can induce T cell responses to the greatest extent .
The follow-up research results of this mRNA cancer vaccine by Merck and Moderna are worth looking forward to.
In addition, in the research and development of personalized antigen vaccines, according to the Wisdom Bud New Drug Information Database, as of July 9, 2023, there are 60 drugs under research for the type of personalized antigen vaccines, including 64 indications.
There are 7 targets, 79 research institutions, and 323 related clinical trials . Personalized antigen vaccines have great potential in many diseases, and we look forward to more good news about such vaccines.
 Official websites of MSD and Moderna
 Merck launched the first phase III clinical trial of tumor mRNA vaccine + K drug. 2023-07-07.
 Nature Series Review: Research Progress and Challenges of Personalized Neoantigen Tumor Vaccines. . 2022-07-28.
 Merck launched the first phase III clinical trial of tumor mRNA vaccine mRNA-4157 combined with K drug for the treatment of melanoma. 2023-07-10.
The world’s first neoantigen mRNA vaccine for personalized tumors.
(source:internet, reference only)