V940-001 is the first Phase 3 study of a planned comprehensive clinical development program being initiated following the positive primary analysis of the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial reported at AACR and ASCO earlier this year

RAHWAY, N.J. & CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Merck (NYSE: MRK), known as MSD outside of the United States and Canada, and Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced the initiation of the pivotal Phase 3 randomized V940-001 clinical trial evaluating V940 (mRNA-4157), an investigational individualized neoantigen therapy (INT), in combination with KEYTRUDA, Merck’s anti-PD-1 therapy, as an adjuvant treatment in patients with resected high-risk (Stage IIB-IV) melanoma. Global recruitment in V940-001 has begun, and the first patients are now enrolling in Australia.

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“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,” said Dr. Marjorie Green, senior vice president and head of late-stage oncology, global clinical development, Merck Research Laboratories. “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.”

“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,” said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. “We thank the patients, investigators, and clinical trial sites across the world for helping us advance our efforts in this area.”

V940-001 is a Phase 3 global, randomized, double-blind, placebo- and active-comparator-controlled study designed to evaluate the safety and efficacy of V940 (mRNA-4157) in combination with KEYTRUDA in people with resected high-risk (Stage IIB-IV) melanoma compared to KEYTRUDA alone. The trial is slated to enroll approximately 1,089 patients at more than 165 sites in over 25 countries around the world. The primary endpoint of the study is recurrence-free survival (RFS), and secondary endpoints include distant metastasis-free survival (DMFS), overall survival (OS), and safety.

Based on data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study, the U.S. Food and Drug Administration 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 (AACR) Annual Meeting and presented the study’s key secondary endpoint, DMFS, in June 2023 at the American Society of Clinical Oncology (ASCO) Annual Meeting. The companies also plan to expand the development program to additional tumor types, including non-small cell lung cancer.

About V940 (mRNA-4157)

V940 (mRNA-4157) is a novel investigational messenger ribonucleic acid (mRNA)-based individualized neoantigen therapy (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 key step in adaptive immunity.

Individualized neoantigen therapies are designed to train and activate the immune system so that a patient can generate an antitumor response specific to their tumor mutation signature. V940 (mRNA-4157) is designed to stimulate an immune response by generating specific T-cell responses based on the unique mutational signature of a patient’s tumor. KEYTRUDA is an immunotherapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Based on early clinical studies and data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial, combining V940 (mRNA-4157) with KEYTRUDA may provide an additive benefit over KEYTRUDA alone.

About V940-001 (NCT05933577)

V940-001 is a global, randomized, double-blind, placebo- and active-comparator-controlled Phase 3 trial evaluating 1,089 patients with resected high-risk (Stage IIB-IV) melanoma. Following complete surgical resection, participants 18 years and older will be randomized 2:1 to receive V940 (mRNA-4157) (1 mg every three weeks for up to nine doses) and KEYTRUDA (400 mg every six weeks up to nine cycles [approximately one year]) versus KEYTRUDA alone for approximately one year until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner. The primary endpoint is RFS, defined as the time from randomization to any type of disease recurrence as assessed by the investigator, or death due to any cause. The secondary endpoints are DMFS, OS, safety and quality of life.

Key eligibility criteria for the trial include: patients who have surgically resected and histologically/pathologically confirmed diagnosis of Stage IIB or IIC, III or IV cutaneous melanoma, patients who have not received any prior systemic therapy for their melanoma beyond surgical resection and no more than 13 weeks have passed between final surgical resection.

For further information, please see: https://clinicaltrials.gov/study/NCT05933577

About melanoma

Melanoma, the most serious form of skin cancer, is characterized by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 325,000 new cases diagnosed worldwide in 2020. In the U.S., skin cancer is one of the most common types of cancer diagnosed, and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be nearly 100,000 new cases of melanoma diagnosed and almost 8,000 deaths resulting from the disease in the U.S. in 2023.

About KEYTRUDA® (pembrolizumab) injection, 100 mg

KEYTRUDA is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD- L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program. There are currently more than 1,600 trials studying KEYTRUDA across a wide variety of cancers and treatment settings. The KEYTRUDA clinical program seeks to understand the role of KEYTRUDA across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with KEYTRUDA, including exploring several different biomarkers.

Selected KEYTRUDA® (pembrolizumab) Indications in the U.S.

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma.

KEYTRUDA is indicated for the adjuvant treatment of adult and pediatric (12 years and older) patients with stage IIB, IIC, or III melanoma following complete resection.

See additional selected KEYTRUDA indications in the U.S. after the Selected Important Safety Information.

Selected Important Safety Information for KEYTRUDA

Severe and Fatal Immune-Mediated Adverse Reactions

KEYTRUDA is a monoclonal antibody that belongs to a class of drugs that bind to either the PD-1 or the PD-L1, blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue, can affect more than one body system simultaneously, and can occur at any time after starting treatment or after discontinuation of treatment. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Early identification and management are essential to ensure safe use of anti–PD-1/PD-L1 treatments. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. For patients with TNBC treated with KEYTRUDA in the neoadjuvant setting, monitor blood cortisol at baseline, prior to surgery, and as clinically indicated. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue KEYTRUDA depending on severity of the immune-mediated adverse reaction. In general, if KEYTRUDA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose adverse reactions are not controlled with corticosteroid therapy.

Immune-Mediated Pneumonitis

KEYTRUDA can cause immune-mediated pneumonitis. The incidence is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.4% (94/2799) of patients receiving KEYTRUDA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (0.9%), and Grade 2 (1.3%) reactions. Systemic corticosteroids were required in 67% (63/94) of patients. Pneumonitis led to permanent discontinuation of KEYTRUDA in 1.3% (36) and withholding in 0.9% (26) of patients. All patients who were withheld reinitiated KEYTRUDA after symptom improvement; of these, 23% had recurrence. Pneumonitis resolved in 59% of the 94 patients.

Pneumonitis occurred in 8% (31/389) of adult patients with cHL receiving KEYTRUDA as a single agent, including Grades 3-4 in 2.3% of patients. Patients received high-dose corticosteroids for a median duration of 10 days (range: 2 days to 53 months). Pneumonitis rates were similar in patients with and without prior thoracic radiation. Pneumonitis led to discontinuation of KEYTRUDA in 5.4% (21) of patients. Of the patients who developed pneumonitis, 42% interrupted KEYTRUDA, 68% discontinued KEYTRUDA, and 77% had resolution.

Pneumonitis occurred in 7% (41/580) of adult patients with resected NSCLC who received KEYTRUDA as a single agent for adjuvant treatment of NSCLC, including fatal (0.2%), Grade 4 (0.3%), and Grade 3 (1%) adverse reactions. Patients received high-dose corticosteroids for a median duration of 10 days (range: 1 day to 2.3 months). Pneumonitis led to discontinuation of KEYTRUDA in 26 (4.5%) of patients. Of the patients who developed pneumonitis, 54% interrupted KEYTRUDA, 63% discontinued KEYTRUDA, and 71% had resolution.

Immune-Mediated Colitis

KEYTRUDA can cause immune-mediated colitis, which may present with diarrhea. Cytomegalovirus infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.7% (48/2799) of patients receiving KEYTRUDA, including Grade 4 (