Merck Launches Second Phase III Trial of Personalized mRNA Cancer Vaccine V940 (mRNA-4157) in Combination with Keytruda for Adjuvant Treatment of Resected Non-Small Cell Lung Cancer

On October 11, MSD initiated the second Phase III clinical trial (V940-002) of its tumor neoantigen mRNA vaccine V940 (mRNA-4157). The first Phase III clinical trial was launched in July this year (see: ).

This study aims to evaluate the efficacy and safety of mRNA-4157 in combination with pembrolizumab (Keytruda, K drug) compared to placebo plus K drug as adjuvant treatment for patients with completely resected stage II, IIIA, and IIIB non-small cell lung cancer (NSCLC).

The study plans to enroll 868 patients with NSCLC, with an expected launch in November this year and completion in June 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 injection, once every 6 weeks). The primary endpoint of the study is disease-free survival (DFS).

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 protein neoantigen mutations, 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 solid tumor patients 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 squamous cell carcinoma of the head and neck 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, 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 recurrence-free survival (RFS), significantly reducing the risk of recurrence or death by 44% in patients. Based on these results, the FDA granted this combination therapy 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 failed, bringing a lot of positive signals to the prospects of tumor applications for mRNA vaccines.

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