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

Phase 2

Recruiting

• Conditions: Melanoma
• Interventions: Drug: mRNA-4157; Biological: Pembrolizumab

• Registration Number: NCT03897881
• Lead Sponsor: ModernaTX, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-03-29
• Study First Submitted QC: 2019-03-29
• Study First Posted: 2019-04-01
• Study Start: 2019-07-18
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-21
• Last Update Posted: 2025-04-23
• Primary Completion: 2029-09-09
• Study Completion: 2029-09-09

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 267

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mRNA-4157 and Pembrolizumab	Pembrolizumab	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.
mRNA-4157 and Pembrolizumab	mRNA-4157	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.
Pembrolizumab	Pembrolizumab	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.

Primary Outcome Measures

Name	Time	Method
Recurrence-Free Survival (RFS), Assessed Using Radiological Imaging	Up to 5 years	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.

Secondary Outcome Measures

Name	Time	Method
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)
Distant Metastasis-Free Survival (DMFS), Assessed Using Radiological Imaging	Up to 5 years	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.

Trial Locations

Locations (22)

University of Arizona; 🇺🇸 Tucson, Arizona, United States

California Pacific Medical Center Research Institute -CPMCRI; 🇺🇸 San Francisco, California, United States

Angeles Clinic and Research Institute; 🇺🇸 Santa Monica, California, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Smilow Cancer Center at Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

Lombardi Cancer Center; 🇺🇸 Washington, District of Columbia, United States

Orlando Health UF Health Cancer Center; 🇺🇸 Orlando, Florida, United States

Northside Hospital; 🇺🇸 Atlanta, Georgia, United States

UPMC Hillman Cancer Center; 🇺🇸 Chicago, Illinois, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States

Hackensack University Medical Center; 🇺🇸 Hackensack, New Jersey, United States

NYU Langone Medical Center; 🇺🇸 New York, New York, United States

Providence Cancer Institute; 🇺🇸 Portland, Oregon, United States

Sarah Cannon Cancer Center; 🇺🇸 Nashville, Tennessee, United States

Texas Oncology PA; 🇺🇸 Dallas, Texas, United States

Melanoma Institute Australia; 🇦🇺 North Sydney, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Princess Alexandra Hospital; 🇦🇺 Woolloongabba, Queensland, Australia

Affinity Clinical Research; 🇦🇺 Murdoch, Western Australia, Australia

St John of God Hospital Subiaco; 🇦🇺 Subiaco, Western Australia, Australia