An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYNOTE-942)

Study Overview
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Brief Summary
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The purpose of this study is to assess whether postoperative adjuvant therapy with mRNA-4157 and pembrolizumab improves recurrence free survival (RFS) compared to pembrolizumab alone in participants with complete resection of cutaneous melanoma and a high risk of recurrence.

Official Title
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A Phase 2 Randomized Study of Adjuvant Immunotherapy With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab Versus Pembrolizumab Alone After Complete Resection of High-Risk Melanoma (KEYNOTE- 942)

Conditions
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Melanoma

Intervention / Treatment
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* Drug: mRNA-4157
* Biological: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Resectable cutaneous melanoma metastatic to a lymph node and at high risk of recurrence Complete resection within 13 weeks prior to the first dose of pembrolizumab Disease free at study entry (after surgery) with no loco-regional relapse or distant metastasis and no clinical evidence of brain metastases Has an formalin fixed paraffin embedded (FFPE) tumor sample available suitable for sequencing Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Normal organ and marrow function reported at screening Key Exclusion Criteria: Prior malignancy, unless no evidence of that disease for at least 5 years prior to study entry Prior systemic anti-cancer treatment (except surgery and interferon for thick primary melanomas. Radiotherapy after lymph node dissection is permitted) Live vaccine within 30 days prior to the first dose of pembrolizumab Transfusion of blood or administration of colony stimulating factors within 2 weeks of the screening blood sample Active autoimmune disease Immunodeficiency, systemic steroid therapy, or any other immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab Solid organ or allogeneic bone marrow transplant Pneumonitis or a history of (noninfectious) pneumonitis that required steroids Prior interstitial lung disease Clinically significant heart failure Known history of human immunodeficiency virus (HIV) Known active hepatitis B or C Active infection requiring treatment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-4157 and Pembrolizumab<br>Participants will receive up to 9 doses of mRNA-4157 (every 21 days). Participants may continue on pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner. | Drug: mRNA-4157<br>* Individualized Neoantigen Therapy<br>Biological: Pembrolizumab<br>* Intravenous infusion<br>|
| Active Comparator: Pembrolizumab<br>Participants will receive pembrolizumab (every 21 days) until disease recurrence, unacceptable toxicity, or they undergo up to 18 total cycles (approximately 1 year of treatment), whichever is sooner. | Biological: Pembrolizumab<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence-Free Survival (RFS), Assessed Using Radiological Imaging | RFS is defined as the time between the date of first dose of pembrolizumab and the date of recurrence (local, regional, or distant metastasis), new primary melanoma, or death (whatever the cause), whichever occurs first. | Up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant Metastasis-Free Survival (DMFS), Assessed Using Radiological Imaging | DMFS is defined as the time between the date of first dose of pembrolizumab and the date of the first distant metastasis or the date of death (whatever the cause), whichever occurs first. | Up to 5 years | 
| Number of Participants With Adverse Events (AEs) |  | Baseline through 100 days after last mRNA-4157 dose (for mRNA-4157 and Pembrolizumab combination arm) and up to 90 days after last pembrolizumab dose (for Pembrolizumab only arm) (up to a total of 5 years for both arms) | 
| Number of Participants Who Discontinued Due to AEs |  | Baseline through 100 days after last mRNA-4157 dose (for mRNA-4157 and Pembrolizumab combination arm) and up to 90 days after last pembrolizumab dose (for Pembrolizumab only arm) (up to a total of 5 years for both arms) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mRNA-4157, Individualized Neoantigen Therapy, INT, Pembrolizumab, Moderna