The Intismeran File.

Phase 3 result · Announced August 19, 2026

A vaccine built for one person just passed its biggest test.

Merck and Moderna announced that intismeran autogene — an mRNA vaccine custom-built from the mutations in each patient's own tumor — combined with the immunotherapy KEYTRUDA, beat KEYTRUDA alone at keeping high-risk melanoma from coming back after surgery. It is the first Phase 3 win for any personalized cancer vaccine — and for any mRNA cancer therapy, ever.[1]

Both endpoints met Confirmed in 1,137-patient Phase 3 Detailed numbers not yet published
1,137 patients enrolled in the Phase 3 INTerpath-001 trial[1]
2 endpoints met: cancer returning near the original site, or spreading to distant organs
1st positive Phase 3 readout for an individualized neoantigen therapy, ever[1]
From tumor fingerprint to wanted poster Concentric arcs representing a tumor's unique mutation fingerprint, an arrow, and a wanted poster listing neoantigen targets, with T-cells approaching. THE TUMOR'S MUTATION FINGERPRINT WANTED UP TO 34 TARGETS T-CELLS, NOW WITH TARGETS
The core idea Every tumor carries a unique set of mutations. Intismeran reads that “fingerprint” and turns it into a personalized wanted poster — up to 34 neoantigen targets — so the patient's immune system knows exactly what to hunt.[1]

01 — What was announced

The headline, minus the hype

On August 19, 2026, Merck and Moderna reported topline results — a first, headline-level look — from INTerpath-001, a large Phase 3 trial. At a pre-planned interim analysis, the combination met both of the goals it was being judged on.[1]

Primary endpoint — met
Recurrence-free survival (RFS) Patients on the combination stayed free of any cancer return — or death — significantly longer than patients on KEYTRUDA alone.[1]
Key secondary endpoint — met
Distant metastasis-free survival (DMFS) The combination significantly delayed the outcome doctors fear most: melanoma reappearing in distant organs.[1]
Who was studied
1,137 patients Completely resected stage IIB–IV cutaneous melanoma, no prior systemic therapy; randomized 2:1, double-blind, placebo-controlled, at sites across 26 countries.[1],[2]
Safety
No new safety signals Side effects were consistent with previous studies of the combination.[1]
Not yet known
Effect size & overall survival The exact Phase 3 hazard ratios, confidence intervals, and p-values have not been disclosed; overall survival data are still maturing.[1],[7]
Regulatory status
Investigational Intismeran is not approved anywhere. The companies say they will present the data at a medical meeting and engage regulators on filings.[1]
What “topline” means — and why it matters for honesty. The companies have announced that the trial succeeded, with independent confirmation that detailed efficacy numbers have not yet been released.[7] Everything quantified on this page comes from the earlier Phase 2b trial (KEYNOTE-942), which is fully published — and is clearly labeled as such wherever it appears.
“Today's results represent a landmark moment for adjuvant melanoma treatment… Intismeran in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.”
Prof. Georgina Long — principal investigator of INTerpath-001; medical director, Melanoma Institute Australia; University of Sydney[1]

02 — Why recurrence is the central fear

Surgery removes the tumor. It can't remove the risk.

Melanoma is the deadliest common skin cancer — an uncontrolled growth of the pigment-producing cells in skin. More than 330,000 people were diagnosed worldwide in 2022, and the numbers have been rising for decades. In the United States alone, about 112,000 new cases and more than 8,500 deaths are expected in 2026.[1]

When melanoma is caught at a high-risk but removable stage (IIB through IV), surgeons can cut it out completely. But “completely resected” describes what a scan can see — not what a few escaped cells might be doing. The danger is recurrence: the cancer returning, most often within the first two years, and in most cases returning as distant metastases — new tumors in the lungs, liver, brain, or elsewhere, which are far harder to treat.[1]

That's why doctors give adjuvant therapy — treatment after surgery, while the patient looks cancer-free. Since the KEYNOTE-054 and KEYNOTE-716 trials, the standard adjuvant option has been KEYTRUDA alone, given for about a year.[1] The question INTerpath-001 answered: can you do meaningfully better than that standard?

Melanoma, in numbers

330,000+ NEW CASES WORLDWIDE, 2022 ~112,000 NEW U.S. CASES EXPECTED IN 2026 8,500+ U.S. DEATHS EXPECTED IN 2026 HIGHEST-RISK WINDOW: FIRST ~2 YEARS AFTER SURGERY risk continues at lower level →
Context Incidence and mortality figures: Merck/Moderna, August 2026.[1] The shaded band marks the qualitative highest-risk window after surgery as described in the release (“most often occurs within the first two years”) — it is not a plotted dataset. Most recurrences are metastatic rather than local.

03 — How the combination works

One drug releases the brakes. The other hands out wanted posters.

The pairing is deliberately complementary. KEYTRUDA (pembrolizumab) is a checkpoint inhibitor: tumors exploit a brake called PD-1 that normally keeps immune T-cells from attacking the body's own tissue. Cancer cells press that brake to hide. KEYTRUDA — a monoclonal antibody — blocks PD-1, so the brake can't be pressed and T-cells stay on the attack.[1]

But releasing a brake only helps if the T-cells know what to aim at. That's the second drug's job. Intismeran is an individualized neoantigen therapy: a synthetic mRNA molecule encoding up to 34 neoantigens chosen from the mutations in that one patient's tumor. Once injected, the patient's own cells read the mRNA, display those fragments, and train squads of T-cells to recognize exactly those targets — a personalized wanted poster for the immune system.[1]

Two jobs, one attack

KEYTRUDA releases the PD-1 brake; intismeran trains T-cells on tumor neoantigens; together they attack Left panel: tumor cell pressing the PD-1 brake on a T-cell, blocked by KEYTRUDA antibodies. Middle panel: intismeran mRNA being translated and presented as wanted posters to T-cells. Right panel: trained, unbraked T-cells converging on a tumor. ① RELEASE THE BRAKES — KEYTRUDA tumor PD-L1 T-cell PD-1 KEYTRUDA KEYTRUDA jams PD-1, so the tumor can't switch the T-cell off. ② ASSIGN THE TARGETS — INTISMERAN mRNA × up to 34 neoantigens APC immune cells present the “wanted posters” target-trained T-cells The vaccine's mRNA is translated in the body and displayed to T-cells — training them on this patient's exact tumor mutations. ③ ATTACK, TOGETHER tumor More T-cells, aimed at the right targets, with their brakes released.
Mechanism, simplified KEYTRUDA is approved medicine; intismeran is investigational. The combination strategy — expand tumor-specific T-cells and unblock them — is why researchers paired the two.[1],[4]

04 — How a personalized vaccine is made

From tumor sample to tailor-made dose, in weeks

There is no warehouse of intismeran — every dose is manufactured for exactly one patient. The Phase 3 protocol required the first treatment dose within 13 weeks of surgery, which bounds the entire biopsy-to-infusion pipeline.[2] Here is the journey each patient's cells take.

Manufacturing pipeline: biopsy, sequencing, neoantigen selection, mRNA design, production, infusion alongside KEYTRUDA A left-to-right flow of six numbered steps with a weeks-after-surgery axis from 0 to 13. week 0 · surgery week 5 week 10 week 13 01 Tumor sample surgical resection 02 DNA sequencing tumor vs healthy tissue 03 Target selection up to 34 neoantigens mRNA 04 mRNA design one synthetic sequence 05 Production & QC a batch of one 06 Injection + KEYTRUDA every 3 weeks, ×9
Figure · the pipeline Six steps from surgery to treatment. The week-13 bound comes from INTerpath-001's eligibility rule: no more than 13 weeks between final surgery and the first dose.[2] Intermediate timings are illustrative; the companies have not published a step-by-step schedule for this trial. Dosing: intismeran 1 mg by intramuscular injection every 3 weeks (up to 9 doses), plus KEYTRUDA 400 mg by IV infusion every 6 weeks (up to 9 cycles, about a year).[1],[2]
  1. Tumor sample. The tumor removed at surgery is preserved for analysis — the raw material of the vaccine.
  2. DNA sequencing. The tumor's genome is compared with the patient's healthy tissue to catalog every mutation — its mutational “fingerprint.”[1]
  3. Target selection. Algorithms flag the mutations most likely to produce neoantigens the immune system can see — up to 34 per patient.[1]
  4. mRNA design. Those targets are encoded into a single synthetic mRNA molecule, unique to this patient.[1]
  5. Production & quality control. The personalized batch is manufactured and tested — a batch of one.
  6. Injection alongside KEYTRUDA. Nine doses over about six months, paired with roughly a year of KEYTRUDA infusions.[1]

05 — The evidence

What the numbers actually show

The Phase 3 result is real but, so far, headline-only: Merck and Moderna say the trial met RFS and DMFS with “statistically significant and clinically meaningful” improvements, and independent coverage confirms the detailed effect sizes have not been disclosed.[1],[7] The hard numbers we do have come from the fully published Phase 2b trial, KEYNOTE-942 — 157 patients with resected stage IIIB–IV melanoma, randomized 2:1 to the same combination (107 patients) versus KEYTRUDA alone (50 patients), now followed for a median of five years.[3],[4] Its primary analysis, published in The Lancet in 2024, found recurrence risk 44% lower with the combination (HR 0.561; 95% CI 0.309–1.017; one-sided p=0.0266), with 18-month recurrence-free rates of 78.6% versus 62.2%.[5] Those data set up — and now have been confirmed by — the Phase 3.

KEYNOTE-942 at five years: how much lower was the risk?

A hazard ratio (HR) of 1.0 would mean the combination changed nothing. Each marker below is the estimated relative risk with the combination; the whiskers are the 95% confidence interval.

Hazard ratios for recurrence, distant metastasis, and death at five years RFS hazard ratio 0.51 (CI 0.294 to 0.887), DMFS 0.411 (CI 0.200 to 0.843), overall survival 0.471 (CI 0.17 to 1.35, crossing 1, exploratory). Reference line at 1.0. ← FAVORS VACCINE + KEYTRUDA FAVORS KEYTRUDA ALONE → 0 0.25 0.5 0.75 1.0 1.25 HAZARD RATIO (COMBINATION vs KEYTRUDA ALONE) 1.0 = NO DIFFERENCE Cancer returns or death (RFS) — primary endpoint HR 0.51 → 49% lower risk 95% CI 0.294–0.887 Cancer spreads to distant organs or death (DMFS) HR 0.41 → 59% lower risk 95% CI 0.200–0.843
Figure · KEYNOTE-942, median 5-year follow-up Recurrence-free survival (RFS) and distant metastasis-free survival (DMFS), combination vs KEYTRUDA alone.[3],[4] Overall survival is deliberately not plotted as a win: its estimate (HR 0.47) came with a confidence interval of 0.17–1.35 that crosses 1.0, with only 14 deaths total (7 per arm) — a promising trend, not a proven survival benefit.[3],[4]

Five years on: 69 vs 49 of 100 still cancer-free

VACCINE + KEYTRUDA · 68.8% ≈ 69 of 100 cancer-free at 5 years KEYTRUDA ALONE · 49.1% ≈ 49 of 100 cancer-free at 5 years
Five-year RFS rates: 68.8% (95% CI 56.3–78.3) vs 49.1% (95% CI 33.3–63.0).[3],[4] Each dot is one representative patient out of 100 (rounded). The confidence intervals are wide — this was a 157-patient trial.

INTerpath-001 (Phase 3): confirmed, not yet quantified

QuestionStatusDetail
Delays cancer's return (RFS) Met — significant “Statistically significant and clinically meaningful” vs KEYTRUDA alone. Effect size not yet disclosed.[1]
Delays distant spread (DMFS) Met — significant Key secondary endpoint, also met at the interim analysis.[1]
Helps patients live longer (OS) Still unknown Trial continues; overall survival is still being evaluated.[1]
Safe enough to use widely No new signals Consistent with prior studies; full safety data still to be presented.[1]
Approved / available Not yet Companies plan to engage regulators on filings; data to be presented at a medical meeting.[1]
Status board The Phase 3 confirms that the combination works in 1,137 patients; the size of the benefit, survival impact, and any approval remain ahead.

06 — How to read “met its endpoint”

A short course in reading trial headlines

“Endpoint” = the finish line set in advance

Before the trial began, the sponsors registered exactly what would count as success: the primary endpoint, RFS (time until cancer returns or the patient dies), and key secondary endpoints including DMFS and overall survival.[2] “Met its endpoint” means the result cleared that pre-agreed bar — not that the cancer is cured.

“Statistically significant” ≠ “big”

Significance means the difference is unlikely to be a fluke of chance. Size is a separate question — that's what the hazard ratio tells you, and for INTerpath-001 the companies have said “clinically meaningful” without yet publishing the number. Both claims will be checkable when the data are presented.

An interim look, with more to come

The readout was a pre-specified interim analysis. The trial itself runs on: overall survival, quality of life, and longer safety follow-up are still being collected, with completion estimated around 2030.[2]

The honest summary: a personalized cancer vaccine has now improved on the standard of care in a large, rigorous, double-blind Phase 3 trial — a genuine first. What we cannot yet say is by how much in that trial, whether it extends life, or when (or whether) regulators will approve it.

07 — How big a deal is this?

Three genuine firsts — with one asterisk

First Phase 3 win for a personalized neoantigen vaccine

Decades of cancer-vaccine attempts had never produced a positive pivotal trial of this kind. INTerpath-001 is the first Phase 3 readout — for any individualized neoantigen therapy — to succeed.[1]

First Phase 3 win for any mRNA cancer therapy

The same mRNA platform behind COVID-19 vaccines has now produced a positive Phase 3 result in oncology — a proof point for an entire technological approach.[1]

First adjuvant regimen to beat KEYTRUDA head-to-head

This is the first Phase 3 study to show a clinically meaningful improvement over KEYTRUDA alone — the current standard — in resected melanoma.[1]

The asterisk: topline announcements are company-reported. The result will be scrutinized — and the effect size revealed — when the full data are presented at a medical meeting and reviewed by regulators. The track record is reassuring: the Phase 2b signal not only held but was sustained through five years of follow-up and peer-reviewed publication.[3]

“By intervening earlier in the course of disease, when many cancers are considered most treatable, the goal of adjuvant therapy given after surgery is to increase the possibility of cure for more patients… We believe individualized neoantigen therapies have the potential to redefine how patients with completely resected stage IIB-IV melanoma are treated.”
Dr. Dean Y. Li — president, Merck Research Laboratories[1]
“For many years, the idea of creating an mRNA treatment designed specifically for an individual patient's cancer was aspirational. We are now helping turn that vision into a reality.”
Stéphane Bancel — CEO, Moderna[1]
“Our study offers strong evidence to melanoma patients that intismeran vaccine therapy, when used in combination with immunotherapy, can demonstrably reduce their risk of having their cancer return.”
Dr. Janice Mehnert — NYU Grossman School of Medicine, senior investigator of the KEYNOTE-942 five-year analysis[4]

08 — What happens next, and what remains unknown

The story so far — and the chapters still unwritten

Timeline of the intismeran program, 2019 to 2030 2019 KEYNOTE-942 begins; 2022 first positive results; 2023 INTerpath-001 starts and first patient dosed; 2024 Lancet publication; June 2026 five-year data at ASCO; August 2026 Phase 3 topline success; 2029-2030 estimated trial completion. 2019 KEYNOTE-942 begins (157 pts) 2022–23 First positive RFS and DMFS signals Jul 2023 INTerpath-001 Phase 3 launches globally 2024 KEYNOTE-942 primary published in The Lancet Jun 2026 5-year data at ASCO: 49% / 59% risk cuts Aug 2026 Phase 3 topline: RFS + DMFS endpoints met → 2030 OS data, full results, regulatory review

Figure · program timeline KEYNOTE-942 dates and results: Lancet 2024 primary publication and 2026 ASCO/JCO five-year update.[3],[5] INTerpath-001 start (July 19, 2023) and estimated completion (2029–2030): ClinicalTrials.gov.[2]

What we know

✓ The combination significantly delayed recurrence and distant spread versus the standard of care in a 1,137-patient, double-blind Phase 3 trial.[1]

✓ The earlier randomized trial showed the benefit persisting at five years, with no new safety signals.[3]

✓ The approach is already being tested across nine Phase 2/3 INTerpath trials in melanoma, lung, bladder, and kidney cancers.[1]

What we don't know yet

? How big the Phase 3 benefit is — hazard ratios and p-values come at the medical meeting presentation.[7]

? Whether patients live longer — overall survival data are still maturing.[1]

? Whether and when regulators approve it — filings are planned, not made.[1]

? Whether it works in other cancers — those INTerpath trials are still reading out.[1]

09 — Sources & references

Every number, traced

This page was built from the primary sources below. Facts were cross-checked across the companies' release, the trial registry, peer-reviewed publications, and independent oncology coverage. Where Phase 3 details are not yet public, the page says so rather than estimating.

  1. [1] Primary source · press release, Aug 19, 2026
    Merck & Moderna. “Merck and Moderna Announce Phase 3 INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA® Met Endpoints of Recurrence-Free Survival (RFS) and Distant Metastasis-Free Survival (DMFS) in Patients With Completely Resected Stage IIB-IV Melanoma.”
    merck.com
  2. [2] Trial registry
    ClinicalTrials.gov: NCT05933577 — “A Phase 3, Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled Clinical Study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab… (INTerpath-001).” Design, eligibility, arms, endpoints, timelines.
    clinicaltrials.gov/study/NCT05933577
  3. [3] Peer-reviewed · five-year data
    Khattak MA, et al. “Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study.” Journal of Clinical Oncology, 2026. DOI: 10.1200/JCO-26-00835.
    pubmed.ncbi.nlm.nih.gov/42223134
  4. [4] Independent oncology coverage · ASCO 2026
    The ASCO Post. “Vaccine Plus Pembrolizumab Reduces Risk of Recurrence in High-Risk, Resected Melanoma” (June 2026). Five-year RFS 68.8% vs 49.1%; DMFS HR 0.41; OS HR 0.47 (exploratory); 7 deaths per arm.
    ascopost.com
  5. [5] Peer-reviewed · primary analysis
    Weber JS, Khattak MA, et al. “Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study.” The Lancet, 2024. RFS HR 0.561 (95% CI 0.309–1.017; one-sided p=0.0266); 18-month RFS 78.6% vs 62.2%.
    thelancet.com
  6. [6] Press release · ASCO 2026 five-year data
    Merck & Moderna. “Moderna and Merck Present 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA®… at the 2026 ASCO Annual Meeting” (June 1, 2026). RFS HR 0.510 (95% CI 0.294–0.887); DMFS HR 0.411 (95% CI 0.200–0.843).
    merck.com
  7. [7] Independent coverage · Phase 3 topline
    OncoDaily. “Merck and Moderna's Intismeran Autogene Plus Keytruda Meets Phase 3 RFS and DMFS Endpoints in Resected Melanoma” (Aug 19, 2026) — confirms detailed Phase 3 efficacy results have not yet been disclosed.
    oncodaily.com
  8. [8] Trial registry · Phase 2b
    ClinicalTrials.gov: NCT03897881 — KEYNOTE-942 / mRNA-4157-P201.
    clinicaltrials.gov/study/NCT03897881

Read this first

This is an independent, educational explainer produced for general readers. It is not medical advice, not affiliated with or endorsed by Merck or Moderna, and not a substitute for consultation with an oncologist. Intismeran autogene is an investigational therapy and is not approved by any regulator. If you or someone you love is facing melanoma, treatment decisions belong with your medical team.

Statistics here describe populations in clinical trials — they cannot predict any individual patient's outcome. Company-reported topline results may be refined when full data are presented and peer-reviewed.

Fonts: Source Serif 4, IBM Plex Sans, IBM Plex Mono (SIL Open Font License). All diagrams are original SVG illustrations drawn for this page from the cited data. No tracking, no cookies.

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