Superficial spreading melanoma

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Moderna and Merck recently announced follow-up data from the phase 2b randomized KEYNOTE-942/mRNA-4157-P201 study, a clinical trial evaluating mRNA-4157 (V940), an investigational individualized neoantigen therapy (INT), in combination with pembrolizumab (Keytruda), Merck's anti-PD-1 therapy, in patients with resected high-risk melanoma (stage III/IV) following complete resection. After a follow-up of 3 years, adjuvant treatment with V940 plus pembrolizumab continued to demonstrate a clinically meaningful improvement in recurrence-free survival (RFS), reducing the risk of recurrence or death by 49% (HR=0.510 [95% CI, 0.288-0.906]; one-sided nominal p=0.0095) compared with pembrolizumab alone. V940 plus pembrolizumab also continued to demonstrate a meaningful improvement in distant metastasis-free survival (DMFS), compared with pembrolizumab alone, reducing the risk of developing distant metastasis or death by 62% (HR=0.384 [95% CI, 0.172-0.858]; one-sided nominal p= 0.0077).

Based on data from the phase 2b 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 plus pembrolizumab for the adjuvant treatment of patients with high-risk melanoma.

"As we continue to follow participants in the KEYNOTE-942/mRNA-4157-P201 study, we are excited to see such a robust clinical benefit with mRNA-4157 (V940) as adjuvant treatment in combination with KEYTRUDA in people with resected high-risk melanoma," said Kyle Holen, MD, the senior vice president and head of development of therapeutics and oncology at Moderna, in the news release. "These data add another positive analysis to the multiple endpoints and subgroups previously assessed in this study. Importantly for this technology, the KEYNOTE-942/mRNA-4157-P201 study was the first demonstration of efficacy for an investigational mRNA cancer treatment in a randomized clinical trial and the first combination therapy to show a significant benefit over KEYTRUDA alone in adjuvant melanoma. We look forward to sharing these data with people impacted by this disease and the broader scientific community."

Adverse events observed with V940 in KEYNOTE-942 are similar to those previously reported. At a median planned follow-up of approximately 3 years, the number of patients reporting treatment-related grade 3 adverse events was similar between the arms (25% for V940 plus pembrolizumab vs 20% for pembrolizumab alone). The most common adverse events associated with V940 were fatigue (60.6%), injection site pain (56.7%), and chills (49%).

In July 2023, Moderna and Merck announced the initiation of a pivotal phase 3 randomized INTerpath-001 (NCT05933577) clinical trial evaluating V940 plus pembrolizumab, as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma. Global recruitment in INTerpath-001 has started.

"We are committed to driving research forward for innovative modalities in earlier stages of cancer, where we can make the most meaningful impact for patients, by combining Merck's expertise in immuno-oncology with Moderna's innovative mRNA technology," said Marjorie Green, MD, the senior vice president and head of late-stage oncology and global clinical development at Merck Research Laboratories, in the news release. "We are pleased to see the results from this planned analyses on recurrence-free survival for V940 (mRNA-4157), and look forward to working with Moderna in expanding our clinical development program for the individualized neoantigen therapy."

Reference

Moderna and Merck announce mRNA-4157 (v940) in combination with Keytruda(r) (pembrolizumab) demonstrated continued improvement in recurrence-free survival and distant metastasis-free survival in patients with high-risk stage iii/iv melanoma following complete resection versus Keytruda at three years. News release. Moderna. December 14, 2023. Accessed December 18, 2023. https://investors.modernatx.com/news/news-details/2023/Moderna-And-Merck-Announce-mRNA-4157-V940-In-Combination-with-KeytrudaR-Pembrolizumab-Demonstrated-Continued-Improvement-in-Recurrence-Free-Survival-and-Distant-Metastasis-Free-Survival-in-Patients-with-High-Risk-Stage-IIIIV-Melanoma-Following-Comple/default.aspx

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Moderna and Merck's V940 Plus Pembrolizumab Demonstrates Improvement in RFS and DMFS in Stage III/IV ... - Dermatology Times