Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study
A newer report of this study has been published: Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study (2026)
- Study type
- Clinical trial
- Study name
- KEYNOTE-942
- Phase
- Phase 2b
- Design
- Randomised, open-label, adjuvant trial with 2:1 randomisation at centres in the USA and Australia
- Sample size
- 157 patients (107 mRNA-4157 + pembrolizumab, 50 pembrolizumab alone)
- Source
- Lancet · 2024
- Trial registration
- NCT03897881
In plain words
After surgery for high-risk melanoma, a year of immunotherapy with pembrolizumab is usually given to lower the chance of the disease coming back. In this study, a personal mRNA “vaccine” was made for each patient based on the specific mutations in their own tumour; it teaches the immune system to recognise those same cancer cells. Patients who received this vaccine together with pembrolizumab had fewer recurrences (22% versus 40%). Side effects were mostly mild (such as tiredness, pain at the injection site and chills). This treatment is still experimental and is only available within clinical trials.
Key results
Treatment arms and regimens
mRNA-4157 (V940; new name: intismeran autogene) 1 mg by intramuscular injection every 3 weeks, maximum 9 doses.
Pembrolizumab 200 mg IV infusion every 3 weeks, maximum 18 doses (about one year), until disease recurrence or unacceptable toxicity.
mRNA-4157 is an investigational drug and has not been approved.
Pembrolizumab 200 mg IV infusion every 3 weeks, maximum 18 doses (about one year), until disease recurrence or unacceptable toxicity.
Source of the regimen details: ClinicalTrials.gov NCT03897881 (maximum 9 doses of mRNA-4157 every 21 days; pembrolizumab up to 18 cycles) and the 5-year update published in J Clin Oncol 2026 (intismeran 1 mg intramuscularly every 3 weeks, 9 doses; pembrolizumab 200 mg IV every 3 weeks, 18 doses)
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 completely resected high-risk stage IIIB to IV cutaneous melanoma. Enrolment ran from 18 July 2019 to 30 September 2021.
Endpoints
Primary endpoint: recurrence-free survival (RFS) in the intention-to-treat population.
Secondary endpoints: distant metastasis-free survival (DMFS) and safety.
Safety and side effects
Most treatment-related adverse events were grade 1 to 2. Treatment-related grade 3 or higher adverse events occurred in 25% of patients in the combination group and 18% in the pembrolizumab group, and no grade 4 or 5 adverse events related to mRNA-4157 were reported. The frequency of immune-mediated adverse events was similar in the two groups (37 patients [36%] versus 18 patients [36%]).
Clinical significance and place in guidelines
KEYNOTE-942 was the first randomised trial to show a benefit of an individualised mRNA-based neoantigen therapy alongside immunotherapy and became the basis for the design of the phase 3 INTerpath-001 trial (NCT05933577). In the 5-year update (JCO 2026), the benefit in recurrence-free survival (HR 0.510) and distant metastasis-free survival (HR 0.411) was maintained. In August 2026 the manufacturers announced that INTerpath-001 had met its primary endpoint (recurrence-free survival) and key secondary endpoint (distant metastasis-free survival), but the numerical phase 3 data have not yet been presented or published in peer-reviewed form as of this writing. mRNA-4157 (intismeran autogene) has not yet been approved by the FDA or EMA and is an investigational treatment.
Limitations
This was a phase 2b, open-label (no placebo) trial with a relatively small sample size; the primary endpoint was borderline significant on a two-sided test (p=0.053) and the confidence interval of the hazard ratio crosses 1. Patients with stage IIB to IIIA were not enrolled and the study was funded by the manufacturers. Confirmation of the results depends on phase 3 trial data.
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.