Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.

Publication Title

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

Authors

• Adnan Khattak
• Matteo S Carlino
• Tarek Meniawy
• George Ansstas
• Matthew H Taylor, Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR USAFollow
• Kevin B Kim
• Meredith McKean
• Georgina V Long
• Ryan J Sullivan
• Mark Faries
• Thuy T Tran
• C Lance Cowey
• Andrew Pecora
• Theresa Medina
• Victoria Atkinson
• Clemens Krepler
• Thomas Jemielita
• Huzhang Mao
• Jacky Chow
• Laureen S Ojalvo
• Janice M Mehnert
• KEYNOTE-942 Investigators

Document Type

Article

Publication Date

6-1-2026

Keywords

oregon; portland; chiles

Abstract

Intismeran autogene (intismeran; formerly V940 or mRNA-4157) is an mRNA-based individualized neoantigen therapy. We report 5-year outcomes of intismeran plus pembrolizumab from the phase IIb KEYNOTE-942 study (ClinicalTrials.gov identifier: NCT03897881). Eligible patients with resected stage IIIB to IV cutaneous melanoma were randomly assigned 2:1 to receive nine doses of intramuscular intismeran 1 mg once every 3 weeks plus 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks or 18 doses of intravenous pembrolizumab 200 mg once every 3 weeks. The primary end point was recurrence-free survival (RFS); secondary end points included distant metastasis-free survival (DMFS) and safety. Five-year analyses were descriptive. Among 157 randomly assigned patients (intismeran plus pembrolizumab, n = 107; pembrolizumab, n = 50), the median planned follow-up at data cutoff (December 15, 2025) was 60.3 (range, 50.5-76.4) months. Intismeran plus pembrolizumab continued to prolong RFS (hazard ratio [HR], 0.510 [95% CI, 0.294 to 0.887) and DMFS (HR, 0.411 [95% CI, 0.200 to 0.843]), with a favorable trend in overall survival (HR, 0.471 [95% CI, 0.165 to 1.345]) versus pembrolizumab. Safety profile continued to be manageable, with no new safety signals. Intismeran plus pembrolizumab was associated with increased T-cell receptor clonality and novel clonotypes versus pembrolizumab; greater novel clone expansion was observed in patients without versus with recurrence in the combination arm. After a 5-year follow-up, intismeran plus pembrolizumab demonstrated sustained, durable treatment benefits versus pembrolizumab alone in resected high-risk melanoma.

Area of Special Interest

Cancer

Specialty/Research Institute

Oncology

Specialty/Research Institute

Dermatology

Specialty/Research Institute

Earle A. Chiles Research Institute

DOI

10.1200/JCO-26-00835