Merck and Moderna announced the initiation of the pivotal phase III, randomized V940-001 clinical trial evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with Keytruda—Merck’s antiprogrammed death receptor-1 (PD-1) therapy—as an adjuvant treatment in patients with resected high-risk (stage IIB-IV) melanoma. Global recruitment in V940-001 has commenced, and the first patients are now registering in Australia.
V940 (mRNA-4157) is a novel, investigational mRNA-based 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. 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.
V940-001 is a phase III global, randomized, double-blind, placebo- and active comparator–controlled study designed to assess the safety and efficacy of V940 (mRNA-4157) in combination with Keytruda in individuals with resected high-risk (stage IIB-IV) melanoma compared with Keytruda alone.
The trial is scheduled to enroll approximately 1,089 patients at more than 165 sites in over 25 countries worldwide. The primary endpoint of the study is recurrence-free survival (RFS), and secondary endpoints include distant metastasis-free survival (DMFS), overall survival, and safety.
Marjorie Green, MD, senior VP and head of late-stage oncology, global clinical development, Merck Research Laboratories, stated, “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. We look forward to continuing to collaborate with Moderna to evaluate this promising new approach with V940 (mRNA-4157) while also building on a standard of care laid by Keytruda.”
Additionally, Kyle Holen, MD, Moderna’s senior VP and head of development, therapeutics, and oncology, stated, “The initiation of the V940-001 Phase 3 trial is an exciting and important milestone for us as we work with our colleagues at Merck and the melanoma patient community to investigate how individualized neoantigen therapy may potentially transform the treatment of the most serious form of skin cancer. We thank the patients, investigators, and clinical trial sites across the world for helping us advance our efforts in this area.”
Based on data from the phase IIb KEYNOTE-942/mRNA-4157-P201 study, the FDA and European Medicines Agency granted Breakthrough Therapy Designation and the Priority Medicines (PRIME) scheme, respectively, for V940 (mRNA-4157) in combination with Keytruda for the adjuvant treatment of patients with high-risk melanoma.
The companies presented the study’s primary endpoint, RFS, in April 2023 at the American Association for Cancer Research Annual Meeting and presented the study’s key secondary endpoint, DMFS, in June 2023 at the American Society of Clinical Oncology Annual Meeting. The companies also plan to increase the development program to additional tumor types, including non–small-cell lung cancer.
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