Personalized mRNA cancer vaccine plus pembrolizumab reduces melanoma recurrence risk in randomized phase 2b trial

Evidence stage: Emerging ClinicalRegulatory status: InvestigationalGuideline status: Not addressed

The randomized, open-label, phase 2b KEYNOTE-942 trial tested an individualized neoantigen therapy — mRNA-4157/V940, a personalized mRNA cancer vaccine manufactured for each individual patient’s own tumor mutations — combined with pembrolizumab, against pembrolizumab alone, as adjuvant (after-surgery) treatment in patients with resected, high-risk (stage IIIB-IV) melanoma. Patients were randomized 2:1 to the combination (107 patients) or pembrolizumab alone (50 patients); after 18 months, recurrence-free survival was 78.6% in the combination arm versus 62.2% with pembrolizumab alone, a 44% reduction in the risk of recurrence or death, published in The Lancet (DOI 10.1016/S0140-6736(23)02268-7). A 3-year update presented at ASCO 2024 (Journal of Clinical Oncology, DOI 10.1200/JCO.2024.42.17_suppl.LBA9512) reported the benefit was sustained. The therapy has received FDA Breakthrough Therapy Designation but is NOT yet FDA-approved for any indication — it remains investigational, currently being tested in the larger, confirmatory phase 3 V940-001/INTerpath-001 trial.

What This Means

In the randomized, phase 2b KEYNOTE-942 trial, adding a personalized mRNA cancer vaccine (manufactured for each patient's own tumor mutations) to pembrolizumab reduced the risk of melanoma recurrence or death by 44% at 18 months compared with pembrolizumab alone (recurrence-free survival 78.6% vs 62.2%), with the benefit reported as sustained at a 3-year follow-up update.

What This Doesn't Mean

This is a randomized phase 2b trial, not yet a confirmatory phase 3 trial -- mRNA-4157/V940 has FDA Breakthrough Therapy Designation but is NOT FDA-approved for any indication and remains investigational, currently being tested in a larger, confirmatory phase 3 trial. This record makes no claim the therapy is currently available outside a clinical trial.

Why It Matters

A genuinely positive, randomized signal for a personalized cancer vaccine -- a fundamentally different therapeutic approach from conventional immunotherapy or targeted therapy -- in a topic area (cancer vaccines) that had no real coverage on this site until now, despite the site's taxonomy already having a dedicated term for it.

Promise & Proof

Proof — strength of the evidence 3 / 5
  • Base score from evidence stage: Emerging Clinical.
Promise — potential significance if later evidence holds up 3 / 5
  • Baseline — a validly-evidenced story starts here; every further point below is an explicit, checkable reason.
  • The record includes substantive editorial reasoning about why this discovery matters.
  • A distinct follow-on/confirmatory study or trial is already cited as a secondary source — the field is already building on this finding.

These two ratings are automatically computed from this story's own structured evidence fields and are shown separately on purpose — they are never combined into one score. They describe this record, not a medical recommendation: they do not establish medical certainty, do not substitute for reading the cited sources, and are recalculated whenever the underlying evidence changes.

Population / Applicability

Studied in: Adults with resected, high-risk (stage IIIB-IV) melanoma, randomized 2:1 to individualized neoantigen therapy mRNA-4157/V940 plus pembrolizumab (107 patients) or pembrolizumab alone (50 patients), in the randomized, open-label, phase 2b KEYNOTE-942 trial. (Adults)

A personalized therapy manufactured individually for each patient's own tumor -- not an off-the-shelf product, and only available within a clinical trial at this evidence stage. This record has not independently reviewed the full safety/tolerability profile, which should be added before publication.

Full evidence details
Study design
Randomized controlled trial
Sample size
157

Funding & Conflicts

Sponsor/developers: Moderna, Inc. and Merck & Co., Inc. (co-development) -- not independently confirmed against a primary corporate-disclosure document.

Regulatory status by jurisdiction

Unspecified jurisdiction

Status
Investigational
Last verified
2026-08-13

This record has no structured cancer-type scope on file yet — editorial review recommended before treating it as applicable to a specific cancer type.

Guideline positions

Guideline

Position
Not addressed
Last verified
2026-08-13

Primary evidence supporting this story

Additional context

Why Should I Trust This?

  • 1 source at Tier 2 — Peer-reviewed primary research, trial registries, regulatory documents, official conference abstracts
  • Last reviewed: 2026-08-13

This panel summarizes real, checkable facts about this record's own sources and review status — it is not a trust score, and reading it is not a substitute for reading the cited sources yourself.

Discovery Timeline

Every recorded change to this record's content or publication status, in order.

  1. Status change — Status changed from "Legacy / Unverified" to "In editorial review".
  2. Status change — Status changed from "In editorial review" to "Verified".

Last reviewed

Related discoveries

Personalized mRNA cancer vaccine plus pembrolizumab reduces melanoma recurrence risk in randomized phase 2b trial

https://cancerdiscoveries.com/discoveries/personalized-mrna-cancer-vaccine-plus-pembrolizumab-reduces-melanoma-recurrence-risk-in-randomized-phase-2b-trial/

Evidence stage: Emerging Clinical

What This Means

In the randomized, phase 2b KEYNOTE-942 trial, adding a personalized mRNA cancer vaccine (manufactured for each patient's own tumor mutations) to pembrolizumab reduced the risk of melanoma recurrence or death by 44% at 18 months compared with pembrolizumab alone (recurrence-free survival 78.6% vs 62.2%), with the benefit reported as sustained at a 3-year follow-up update.

What This Doesn't Mean

This is a randomized phase 2b trial, not yet a confirmatory phase 3 trial -- mRNA-4157/V940 has FDA Breakthrough Therapy Designation but is NOT FDA-approved for any indication and remains investigational, currently being tested in a larger, confirmatory phase 3 trial. This record makes no claim the therapy is currently available outside a clinical trial.

Why It Matters

A genuinely positive, randomized signal for a personalized cancer vaccine -- a fundamentally different therapeutic approach from conventional immunotherapy or targeted therapy -- in a topic area (cancer vaccines) that had no real coverage on this site until now, despite the site's taxonomy already having a dedicated term for it.

Primary sources

  • Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study (The Lancet) — https://doi.org/10.1016/S0140-6736(23)02268-7 (DOI 10.1016/S0140-6736(23)02268-7)

Date verified: 2026-08-13

Correction status: No correction or retraction