Merck and Moderna Launch First Phase III Trial of Personalized mRNA Cancer Vaccine V940 (mRNA-4157) in Combination with Keytruda for High-Risk Melanoma

Recently, Moderna has been gaining significant attention. On July 5, the world's first mRNA RSV vaccine was submitted for marketing by Moderna; on the same day, Moderna's subsidiary, VirtueRNA Bio, settled in Shanghai, joining the competition in China’s vaccine industry. Yesterday, Moderna’s partner MSD (Merck & Co., Inc.) initiated the first Phase III clinical trial (V940-001) of the tumor neoantigen mRNA vaccine V940 (mRNA-4157). With advances in COVID-19, RSV, and cancer vaccines, the mRNA vaccine field seems to be really heating up.

The V940-001 study, launched this time, was part of MSD's plan finalized in December last year. The study aims to evaluate the efficacy and safety of mRNA-4157 in combination with pembrolizumab (Keytruda, K drug) compared to placebo plus K drug in patients with high-risk Stage II-IV melanoma who have not received systemic treatment.

The V940-001 study plans to enroll 1,089 patients with melanoma, with an expected start in August this year and completion in September 2030. Patients in the experimental group will receive up to 9 doses of mRNA-4157 (intramuscular injection, once every 3 weeks) and up to 9 doses of Keytruda (intravenous infusion, once every 6 weeks), while those in the control group will receive placebo and Keytruda treatment. The primary endpoint of the study is recurrence-free survival (RFS).

mRNA-4157 is a personalized tumor neoantigen vaccine developed by Moderna for each cancer patient's unique tumor mutations. It enhances T-cell immune responses to endogenous neoantigens and induces epitope spreading to new antigens capable of driving anti-tumor responses.

Source: Moderna Official Website

The preparation process of mRNA-4157 takes approximately 6 weeks, including four steps: extraction of tumor tissue and blood samples, sequencing to identify neoantigen mutations in proteins, designing mRNA sequences expressing neoantigens (up to 34 types), and production.

In June 2016, MSD invested $200 million as an upfront payment in Moderna to develop mRNA-4157. In August 2017, mRNA-4157 entered Phase I clinical trials for the first time (KEYNOTE-603). Two years later, Moderna reported positive results: among 20 patients with solid tumors who received at least one dose of mRNA-4157 (0.04-1.0mg) and Keytruda treatment, 6 achieved objective responses.

In November 2020, the HPV-negative subgroup of head and neck squamous cell carcinoma in the KEYNOTE-603 study also achieved positive progress. Among 10 patients receiving combination therapy, 5 achieved objective response, with PFS reaching 9.8 months, showing better results compared to the previous Keytruda monotherapy group (14.6% objective response rate, PFS only 2.0 months).

In December 2022, MSD announced that the Phase IIb study (KEYNOTE-942) of mRNA-4157 in combination with Keytruda (K药) as adjuvant therapy for completely resected stage III/IV melanoma met the primary endpoint of RFS, significantly reducing the risk of recurrence or death by 44% in patients. Based on the results of this study, the FDA granted the combination Breakthrough Therapy Designation in February this year, and the EMA granted it Priority Medicines (PRIME) designation in April this year.

Source: Moderna Official Website

It can be said that mRNA-4157 has had a smooth journey so far, with funding supported by MSD, and its efficacy data has never disappointed, bringing a lot of positive signals for the application prospects of mRNA vaccines in cancer treatment.

By contrast, BioNTech, another major player in the mRNA vaccine field, has been much quieter. Currently, four of BioNTech's tumor mRNA vaccines are in Phase II clinical trials, with its earliest candidate, BNT111, having seen no disclosed clinical progress updates for two years. However, BioNTech has continued to introduce various tumor mRNA vaccines, with 10 related products now undergoing clinical research in its pipeline. Compared to rushing a single vaccine to market, the company seems to prefer advancing on multiple fronts simultaneously.

Copyright © 2023 PHARMCUBE. All Rights Reserved.

Welcome to forward, share, and reasonably cite. When citing, please clearly indicate the source of the article; if you need to reprint, please leave a message to the WeChat Official Account backend or send a message, and include the name and ID of the official account.

Disclaimer: The information in this WeChat article is for general reference only and should not be used directly as decision-making content. PharmaCube assumes no responsibility for any loss incurred by any party due to the use of the content herein.

Exciting Preview

Online Live Streaming & Offline Salon