# KEYNOTE-942: a personalised mRNA cancer vaccine plus pembrolizumab after melanoma surgery

Source: https://onco.cc/key-papers/paper-keynote-942-lancet-2024/  
OnCo record `paper-keynote-942-lancet-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A vaccine custom-made from each patient's own tumour mutations, given with pembrolizumab after surgery for high-risk melanoma, reduced recurrence by about 44% compared with pembrolizumab alone in a mid-sized randomised trial, the first sign that personalised cancer vaccines can work.

## Summary

Open-label randomised phase 2b trial of 157 patients with completely resected stage IIIB-IV melanoma randomised 2:1 to mRNA-4157 (V940, intismeran autogene, encoding up to 34 patient-specific neoantigens) plus pembrolizumab or pembrolizumab alone for about a year. Primary endpoint was recurrence-free survival.

Recurrence-free survival HR was 0.56 (18-month RFS 78.6% vs 62.2%) and distant metastasis-free survival HR 0.35, with benefit regardless of tumour mutational burden or PD-L1. Toxicity was mainly injection-site reactions and flu-like symptoms. It triggered the phase 3 INTerpath-001 trial and a wave of investment in individualised neoantigen vaccines.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: The Lancet
- Year: 2024
- DOI: 10.1016/S0140-6736(23)02268-7
- Authors: Weber JS, Carlino MS, Khattak A, et al.
- Findings: Recurrence-free survival HR 0.561 (95% CI 0.309-1.017); 18-month RFS 78.6% vs 62.2%.; Distant metastasis-free survival HR 0.347 (95% CI 0.145-0.828).; Benefit was seen in both high and low tumour mutational burden and in PD-L1-negative tumours.; Three-year update: RFS HR 0.51, with the curves continuing to separate.; Grade 3 or higher treatment-related adverse events 25% vs 18%; vaccine-related events were mostly grade 1-2 fatigue, injection-site pain and chills.; Manufacturing took about six to eight weeks per patient from biopsy sequencing to first dose.
- What it means: For the first time a randomised trial suggests that a vaccine tailored to an individual's tumour can reduce relapse when combined with immunotherapy, which is a proof of concept for a field that had failed for decades. Nothing changes for patients yet: the trial was small, the confidence interval crossed one, and the phase 3 trial in melanoma (and parallel trials in lung and other cancers) must confirm it. If it does, personalised mRNA vaccines could become a routine adjunct to checkpoint inhibitors after surgery.
- Caveats: Phase 2b with 157 patients and an upper confidence limit above 1.0; the prespecified one-sided p-value was met but the result needs confirmation.; Open-label; recurrence assessments were investigator-based.; Individualised manufacturing is slow and expensive and has never been scaled to thousands of patients.; No biomarker predicts who benefits, and the mechanism (neoantigen-specific T-cell expansion) has been shown in only a subset.

## Sources

- PubMed search: KEYNOTE-942 mRNA-4157 Lancet 2024: https://pubmed.ncbi.nlm.nih.gov/?term=mRNA-4157+V940+pembrolizumab+melanoma+KEYNOTE-942+Lancet
- ClinicalTrials.gov NCT03897881: https://clinicaltrials.gov/study/NCT03897881

## Connected records

- cancers: [Melanoma](https://onco.cc/cancers/melanoma/)
- technologies: [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/), [Personalised neoantigen (mRNA) vaccines](https://onco.cc/technologies/neoantigen-mrna-vaccine/), [Whole-exome & whole-genome sequencing](https://onco.cc/technologies/wes-wgs/)
- targets: [PD-1](https://onco.cc/targets/pd1/)
- drugs: [Intismeran autogene](https://onco.cc/drugs/intismeran-autogene/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Merck & Co. (MSD)](https://onco.cc/companies/merck/), [Moderna](https://onco.cc/companies/moderna/)
- terms: [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Neoantigen](https://onco.cc/terms/neoantigen/), [Tumour mutational burden (TMB)](https://onco.cc/terms/tmb/)
- trials: [An Efficacy Study of Adjuvant Treatment With the Personalized Cancer Vaccine mRNA-4157 and Pembrolizumab in Participants With High-Risk Melanoma (KEYN](https://onco.cc/trials/nct03897881/), [INTerpath-001 (V940-001)](https://onco.cc/trials/interpath-001/)
- people: [Jeffrey S. Weber](https://onco.cc/people/jeffrey-weber/), [Ryan J. Sullivan](https://onco.cc/people/ryan-sullivan/)
- bottlenecks: [Manufacturing cost and time for living and radioactive medicines](https://onco.cc/bottlenecks/b-manufacturing-cell-therapy/), [No one can predict who responds to immunotherapy](https://onco.cc/bottlenecks/b-immunotherapy-response/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [The Lancet](https://onco.cc/journals/lancet/)

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