Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study
- Study type
- Clinical trial
- Study name
- KEYNOTE-942
- Phase
- Phase 2b
- Design
- Randomised, open-label, adjuvant trial with 2:1 randomisation; descriptive 5-year analyses
- Sample size
- 157 patients (107 intismeran + pembrolizumab, 50 pembrolizumab)
- Source
- J Clin Oncol · 2026
- Trial registration
- NCT03897881
In plain words
This report looked again at the same patients from the KEYNOTE-942 study about 5 years after treatment started. The key finding is that the effect of the personal mRNA vaccine in lowering the chance of melanoma coming back has not faded over time: the risk of recurrence or death was about 49% lower, and the risk of the disease spreading to distant parts of the body about 59% lower. The data on overall survival are encouraging but not yet conclusive. No new side effects were seen over these years. This treatment is still experimental.
Key results
Treatment arms and regimens
Intismeran autogene 1 mg by intramuscular injection every 3 weeks, 9 doses, with pembrolizumab 200 mg IV every 3 weeks, 18 doses.
Intismeran is an investigational drug and has not been approved.
Pembrolizumab 200 mg IV every 3 weeks, 18 doses.
Source of the regimen details: Abstract of the published paper (J Clin Oncol 2026) and ClinicalTrials.gov NCT03897881
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with resected stage IIIB to IV cutaneous melanoma. Median planned follow-up at data cut-off (15 December 2025) was 60.3 months (range 50.5–76.4).
Endpoints
Primary endpoint: recurrence-free survival (RFS).
Secondary endpoints: distant metastasis-free survival (DMFS) and safety; overall survival and T-cell receptor analyses as exploratory/descriptive.
Safety and side effects
The safety profile remained manageable, and no new safety signal was seen at 5-year follow-up.
Clinical significance and place in guidelines
This update shows the durability of the benefit of individualised neoantigen therapy over long follow-up, but the analyses are descriptive. According to the manufacturers' announcement (August 2026), the phase 3 INTerpath-001 trial (NCT05933577) in resected stage IIB to IV melanoma has met its primary endpoint of recurrence-free survival and its secondary endpoint of distant metastasis-free survival; its numerical data have not yet been presented or published in peer-reviewed form. Intismeran autogene has not yet been approved by the FDA or EMA.
Limitations
The 5-year analyses are descriptive, without control of type I error. The study is open-label, phase IIb and small (in particular 50 patients in the control group), and the confidence interval of the overall survival hazard ratio crosses 1. The study was funded by the manufacturers.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.