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

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.

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Publication Details

Journal
JCO oncology advances.
Published
2026-02-01
DOI
https://doi.org/10.1200/oa-25-00008
Primary Topic
Cutaneous Melanoma Detection and Management
Type
article
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article

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

Meredith McKean, R Sullivan, Lakshmi Srinivasan, Geoffrey T. Gibney et al.
JCO oncology advances.
Cutaneous Melanoma Detection and Management
article

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

Meredith McKean, R Sullivan, Lakshmi Srinivasan, Geoffrey T. Gibney, M. Mooradian, Matthew H. Taylor, Tracey Posadas, Jennifer Segar, Jeffrey S. Weber, G. Ansstas, Kevin Kim, Julie R. Howle, Sajeve Thomas, Azim Khan, Victoria Atkinson, Montaser Shaheen, Robert Meehan, M. Huang, Igor Feldman, Tal Zaks, Jia Guo, Omid Hamid, A L Pecora, Huzhang Mao, Jane A Healy, Jason Luke, Min Lu, Janice M. Mehnert, Matteo S. Carlino, Elizabeth I. Buchbinder, Thuy T. Tran, Mark Faries, Tarek Meniawy, C. Lance Cowey, Michelle Brown, Wei Zheng, Georgina V. Long, Theresa Medina, Manju Morrissey, Anjali Rao, Adnan Khattak, Lili Zhu, Vasudha Sehgal
article en

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.

JCO oncology advances.(3)
Merck & Co., Inc., Rahway, NJ, USA (United States) (US), St John of God Subiaco Hospital (AU), The University of Sydney (AU), Hackensack University Medical Center (US), Harvard University (US), University of Arizona (US), Orlando Health (US), The University of Texas at San Antonio Health Science Center (US), Washington University in St. Louis (US), Royal North Shore Hospital (AU), Texas Oncology (US), Hollywood Private Hospital (AU), Providence Portland Medical Center (US), California Pacific Medical Center (US), Princess Alexandra Hospital (AU), Blacktown & Mount Druitt Hospital (AU), NYU Langone Health (US), Massachusetts General Hospital (US), Sarah Cannon (US), Angeles Clinic and Research Institute (US), Moderna Therapeutics (United States) (US), Dana-Farber Cancer Institute (US), Melanoma Institute Australia (AU), UPMC Hillman Cancer Center (US), University of Colorado Cancer Center (US), Smilow Cancer Hospital (US), Georgetown Lombardi Comprehensive Cancer Center, University of Colorado Denver (US)
Openalex Percentile: Top 57%
Cutaneous Melanoma Detection and Management
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