Phase 3 Trial Underway for Novel Pembrolizumab Combination for Treatment of High-Risk Melanoma

Merck and Moderna, Inc have announced the initiation of the phase 3, randomized V940-001 (NCT05933577) clinical trial, which is evaluating the safety and efficacy of pembrolizumab (Keytruda; Merck) plus the individualized neoantigen therapy (INT) V940 (mRNA-4157) as an adjuvant therapy regimen for patients with resected high-risk (stage 2B-4) melanoma, according to a Moderna press release. In previous clinical trials, the novel combination displayed greater benefits than pembrolizumab alone.

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“As we continue our efforts to advance novel treatment options for patients with high-risk stage 2B-4 melanoma, the initiation of the V940-001 phase 3 trial represents an important step forward in these efforts and our study of INT,” said Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories, in the press release.

V940 (mRNA-4157) is a novel investigational messenger ribonucleic acid (mRNA)-based INT that represents adaptive immunity. Similar to other INTs, the novel treatment is designed in a way that allows the patient’s immune system to generate an antitumor response that is highly specific to their unique tumor mutation signature, according to investigators. Paired with pembrolizumab, an anti-PD-1 therapy designed to enhance the immune system’s ability to fight tumor cells, the duo may amplify anti-tumor response compared to pembrolizumab alone.

V90-001 is a global, randomized, double-blind, placebo- and active-comparator-controlled study that plans to enroll 1089 patients with resected, high-risk (stage 2B-4) melanoma across 165 sites worldwide. The primary endpoint of recurrence-free survival (RFS) was announced in April 2023 at the American Association for Cancer Research (AACR) Annual Meeting. Secondary endpoints—distant metastasis-free survival (DMFS), overall survival (OS), and safety—were announced in June 2023 at the American Society of Clinical Oncology (ASCO) Annual Meeting.

In other clinical trials, the most common adverse events (AEs) associated with pembrolizumab were fatigue and nausea, with other commonly reported AEs including diarrhea, rash, constipation, and respiratory issues, which includes cough.

Melanoma is a severe form of skin cancer that is associated with the highest number of skin cancer-related deaths. Distinguishable by the uncontrolled growth of pigment-producing cells, diagnoses of the disease continue to climb in the United States.

The FDA already granted Breakthrough Therapy Designation to V940 (mRNA-4157) and pembrolizumab for the adjuvant treatment of high-risk melanoma, based on the phase 2b KEYNOTE-942/mRNA-4157-P201 study. Pembrolizumab is indicated for the treatment of unresectable or metastatic melanoma and stages 2B-3 melanoma following resection in adults and pediatric patients. Indications for other tumor types include lung cancer, lymphoma, gastric cancer, and renal cell carcinoma.

“We look(s) 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 [pembrolizumab],” Green said in the press release.

Reference

MERCK AND MODERNA INITIATE PHASE 3 STUDY EVALUATING V940 (MRNA-4157) IN COMBINATION WITH KEYTRUDA® (PEMBROLIZUMAB) FOR ADJUVANT TREATMENT OF PATIENTS WITH RESECTED HIGH-RISK (STAGE IIB-IV) MELANOMA. Moderna. July 26, 2023. Accessed on July 27, 2023. https://investors.modernatx.com/news/news-details/2023/Merck-and-Moderna-Initiate-Phase-3-Study-Evaluating-V940-mRNA-4157-in-Combination-with-KEYTRUDA-pembrolizumab-for-Adjuvant-Treatment-of-Patients-with-Resected-High-Risk-Stage-IIB-IV-Melanoma/default.aspx