Source – Merck
Moderna and Merck announced the commencement of the pivotal Phase III randomized V940-001 clinical trial. This trial aims to evaluate the effectiveness of V940 (mRNA-4157), an investigational personalized neoantigen therapy (INT), when used in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, as an adjuvant treatment for patients with resected high-risk (Stage IIB-IV) melanoma. The recruitment process for V940-001 has already commenced globally, with the first patients enrolling in Australia.
“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 III 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.”
– Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories
“The initiation of the V940-001 Phase III 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.”
– Kyle Holen, M.D., Moderna’s Senior Vice President and Head of Development, Therapeutics and Oncology
V940-001 is a Phase III global trial that follows a randomized, double-blind, placebo- and active-comparator-controlled design. Its primary objective is to assess the safety and efficacy of V940 (mRNA-4157) in combination with KEYTRUDA, compared to KEYTRUDA alone, in individuals with resected high-risk melanoma (Stage IIB-IV). The trial plans to enroll approximately 1,089 patients across more than 165 sites in over 25 countries worldwide. Key endpoints include recurrence-free survival (RFS), as well as distant metastasis-free survival (DMFS), overall survival (OS), and safety, among others.
V940 (mRNA-4157) has received Breakthrough Therapy Designation from the US Food and Drug Administration and the Priority Medicines (PRIME) scheme from the European Medicines Agency based on data from the Phase IIb
KEYNOTE-942/mRNA-4157-P201 study. These regulatory recognitions were granted for the combination of V940 with KEYTRUDA as an adjuvant treatment for high-risk melanoma patients. The companies presented the primary endpoint data (RFS) at the American Association for Cancer Research (AACR) Annual Meeting in April 2023 and the key secondary endpoint data (DMFS) at the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2023. Additionally, the companies have future plans to expand the development program to include other tumor types, such as non-small cell lung cancer.
V940 (mRNA-4157) is an innovative mRNA-based personalized neoantigen therapy (INT) that involves a synthetic mRNA coding for up to 34 neoantigens. These neoantigens are uniquely tailored to each patient’s tumor DNA sequence through an algorithmic process. Upon administration, the RNA-encoded neoantigen sequences are naturally processed and presented within the patient’s cells, facilitating adaptive immunity—a crucial step in the therapeutic approach.
