Three-Year Update of a Randomized Phase IIb Study of the Individualized Neoantigen Therapy Intismeran Autogene (mRNA-4157, V940) Plus Pembrolizumab Versus Pembrolizumab in Resected Melanoma
Year: 2026
Type: article
Study design: Clinical Trial
Abstract: PURPOSE Primary analysis of KEYNOTE-942 (ClinicalTrials.gov identifier: NCT03897881 ) demonstrated prolonged recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) for the individualized neoantigen therapy intismeran autogene (intismeran; formerly mRNA-4157 or V940) with pembrolizumab versus pembrolizumab alone in high-risk resected melanoma. This update provides an additional year of follow-up to assess longer-term efficacy/safety. METHODS KEYNOTE-942 is a phase IIb study in patients with completely resected high-risk (stage IIIB to IV) cutaneous melanoma who were randomly assigned to receive either intismeran plus pembrolizumab or pembrolizumab alone. The primary end point was RFS; secondary end points included DMFS and safety/tolerability. Overall survival and biomarker data were exploratory. RESULTS With a median follow-up of approximately 3 years, and a minimum of approximately 2 years (median [range] 34.9 [25.1-51.0] months), the combination continued to demonstrate improvement in RFS (hazard ratio [HR], 0.510 [80% CI, 0.351 to 0.743]) and DMFS (HR, 0.384 [80% CI, 0.227 to 0.650]) compared with pembrolizumab. The safety profile was consistent with earlier findings. Most adverse events (AEs) were low-grade, with serious AEs, immune-related AEs, and grade 3/4 events comparable between the arms and no grade 4/5 events related to intismeran. CONCLUSION Intismeran plus pembrolizumab significantly prolongs RFS and DMFS compared with pembrolizumab alone for the adjuvant treatment of resected high-risk melanoma.
Source: JCO oncology advances.
DOI: 10.1200/oa-25-00008
Authors: Matteo S. Carlino, Adnan Khattak, Tarek Meniawy, George Ansstas, Matthew H. Taylor, Kevin B. Kim, Meredith McKean, Georgina V. Long, Ryan J. Sullivan, Mark Faries, Thuy T. Tran, C. Lance Cowey, Andrew Pecora, Montaser Shaheen, Jennifer Segar, Theresa Medina, Victoria Atkinson, Geoffrey T. Gibney, Jason J. Luke, Sajeve Thomas, Elizabeth I. Buchbinder, Omid Hamid, Jeffrey S. Weber, Meghan J. Mooradian, Julie Howle, Azim Khan, Mo Huang, Jane Healy, Manju Morrissey, Igor Feldman, Vasudha Sehgal, Min Lu, Anjali Rao, Wei Zheng, Lakshmi Srinivasan, Huzhang Mao, Jia Guo, Lili Zhu, Tracey Posadas, Michelle Brown, Tal Zaks, Robert S. Meehan, Janice M. Mehnert
Institutions: The University of Sydney, Melanoma Institute Australia, Edith Cowan University, Hollywood Private Hospital, St John of God Subiaco Hospital, Washington University in St. Louis, Providence Portland Medical Center, California Pacific Medical Center, Sarah Cannon, Royal North Shore Hospital, Harvard University, Massachusetts General Hospital, Angeles Clinic and Research Institute, Yale New Haven Hospital, Smilow Cancer Hospital, Texas Oncology, Hackensack University Medical Center, The University of Texas at San Antonio Health Science Center, University of Arizona, University of Colorado Cancer Center, Princess Alexandra Hospital, Georgetown Lombardi Comprehensive Cancer Center, UPMC Hillman Cancer Center, Orlando Health, Dana-Farber Cancer Institute, NYU Langone’s Laura and Isaac Perlmutter Cancer Center, Merck & Co., Inc., Rahway, NJ, USA (United States)
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W7128727502