Top KOLs Discussing INTerpath-001
INTerpath-001 Key Slides & Visuals
INTerpath-001 Top Tweets
𝕏The mRNA vaccine success vs melanoma in a Phase definitive 3 randomized trial today is on top of signs of success for personalized mRNA neoantigen vaccines vs pancreatic cancer, triple negative breast cancer, and non-small cell lung cancer https://t.co/cv4iXW11mw
𝕏Positive phase 3 data for adjuvant pembro +/- personalized mRNA-based neoantigen vaccine for melanoma just announced by Merck and Moderna. Welcome to the future! https://t.co/rlKAvv7sbo https://t.co/BxYKh4NKKw
𝕏JUST IN and via @Merck + @moderna_tx: A landmark moment for cancer immunotherapy. 🎯 Phase 3 INTerpath-001 is positive: the individualized mRNA neoantigen therapy intismeran (V940/mRNA-4157) + pembrolizumab significantly improved both RFS/DMFS vs pembrolizumab alone after resection of high-risk melanoma. For years, the idea of designing a treatment around the unique mutations of each patient’s tumor seemed aspirational. Now we have the first positive Phase 3 trial (N=1137) of an individualized neoantigen therapy—and of an mRNA-based cancer therapy. Personalized cancer vaccines are moving from promise to reality. Now we need to see the magnitude of benefit, durability, and ultimately OS. But today is an important day for the field—and hopefully for our patients. 👏 Congrats to #CathyWu @DanaFarber for her trailblazing research that is materializing in tangible outcomes! At @DanaFarber_GU we are closely working with Cathy + @DFCI_NeoVax team on several GU protocols, after our @Nature work with @BraunMDPhD et al (https://t.co/BdbKJqMKOw) https://t.co/Akd0XQt3ml
𝕏Personalized mRNA-based neoantigen vaccines + pembo are being tested in a number of randomised adjuvant cancer trials (included bladder and renal). The 1st positive trial (RIII in melanoma) was announced today. PCVs are logistically complex with limited monotherapy activity in advanced disease, but early IO combinations in MRD may overcome tumor microenvironment resistance. Patient selection or even vaccine generation could occur with ctDNA. @OncoAlert https://t.co/FUC1sDu3pn
𝕏Are you into Intismeran- the new “individualized neoantigen therapy” (graciously avoiding the term “vaccine”) from Merck/Moderna? If you haven’t- you should! Maybe biggest news in onc for some time along w daraxonrasib- positive results in pivotal melanoma trial as to RFS improvement of this Space age technology which still makes my head spin- whole genome seq- neoantigen selection- personalized “INT” delivered to your patient in just a few weeks… and it works! Many studies ongoing in lung/bladder etc- eager to learn results (and continue to offer to our pts at Monte @BrendonStilesMD !) Now Back to the Future and let’s keep enrolling!
𝕏Huge news in personalized cancer vaccine space this morning.* * awaiting full release of data. Moderna and Merck say mRNA cancer vaccine succeeded in late-stage melanoma trial https://t.co/3Il37x9Rr9 @Perlmutter_CC @JaniceM10
𝕏🔥INTerpath-001: "Statistically significant and clinically meaningful improvements in RFS and DMFS" 🆙 @Merck @moderna_tx 👥Patients: Completely resected stage IIB-IV cutaneous melanoma, no prior systemic therapy 3⃣Phase III ⚖️Intismeran autogene (mRNA-4157) + pembrolizumab ⚖️Pembrolizumab alone (+ placebo) 🔢NCT05933577 @OncoAlert @Larvol 🔗 https://t.co/gwh3BHxVNI
𝕏Next step lung cancer? Adjuvant personalized vaccine improves outcomes in resected melanoma. Trials either fully accrued or ongoing in lung! #lcsm https://t.co/zqOeKTH2Nl
𝕏Personalized cancer vaccines crossed a major line. Phase 3 INTerpath-001 is positive in resected melanoma. We also participated in the adjuvant RCC trial and are looking forward to seeing its results. @OncoAlert @ONCOassist @OpenMedicineHQ @AnkaraUni @Ankaratip1945 https://t.co/poRpkCiF4V
𝕏⭐️🚨 Moderna and Merck say mRNA cancer vaccine succeeded in late-stage melanoma trial. ⭐️So-called “neoantigen” vaccines have long been seen as having potential as cancer treatments, but this is the first randomized Phase 3 clinical trial aimed at definitively proving their benefit. In this case the personalized vaccine, intismeran, was combined with Merck’s Keytruda in adjuvant melanoma, meaning patients’ disease had been surgically removed @OncoAlert https://t.co/5em9OgrOdQ via @statnews
About the INTerpath-001 Trial
Intismeran autogene is an mRNA-based individualized neoantigen therapy: each patient’s resected tumor is sequenced, up to 34 tumor-specific neoantigens are selected, and a single mRNA encoding them is manufactured for that patient, then given with pembrolizumab. INTerpath-001 tested this combination against pembrolizumab alone as adjuvant therapy in completely resected stage IIB–IV cutaneous melanoma.
On August 19, 2026 the trial met both its primary endpoint (recurrence-free survival) and key secondary endpoint (distant metastasis-free survival) with statistically significant, clinically meaningful improvements — the first positive Phase 3 for an individualized neoantigen therapy. Sibling INTerpath trials are ongoing in NSCLC, bladder cancer and first-line advanced melanoma. Principal investigator Professor Georgina Long (Melanoma Institute Australia) said the combination “has the potential to establish a new treatment paradigm in the adjuvant melanoma setting.” Magnitude of benefit has not been disclosed; data will be presented at an upcoming medical meeting and OS follow-up continues.
Trial Methodology & Results
Study Design
Randomized (2:1), double-blind, placebo- and active-comparator-controlled global Phase 3. 1,137 patients enrolled following complete surgical resection.
Population
Completely resected, high-risk stage IIB–IV cutaneous melanoma; no prior systemic therapy.
Interventions
Intismeran autogene 1 mg IM q3w (up to 9 doses) + pembrolizumab 400 mg q6w (up to 9 cycles, ~1 year) vs placebo + pembrolizumab.
Endpoints
Primary: recurrence-free survival (RFS). Key secondary: distant metastasis-free survival (DMFS). Other secondary: OS, safety, quality of life (EORTC QLQ-C30).
Manufacturing
Each dose is patient-individualized: tumor + blood sequencing → neoantigen selection → single-mRNA manufacture → IM administration (see Dr. Tarhini’s workflow slide above).
Sponsors
Merck Sharp & Dohme (sponsor) with ModernaTX (collaborator); intismeran jointly developed by Merck and Moderna.
Topline efficacy (announced Aug 19, 2026 — numbers pending presentation)
Statistically significant and clinically meaningful improvements in BOTH recurrence-free survival (primary) and distant metastasis-free survival (key secondary) versus pembrolizumab alone. Effect sizes, confidence intervals and event counts have not been disclosed and will be presented at an upcoming international medical meeting; the trial continues per protocol to evaluate overall survival.
First positive Phase 3 for an individualized neoantigen therapySource: Merck/Moderna topline press release
Clinical Implications
⚠ Investigational. If the presented magnitude holds up, adjuvant melanoma would gain its first individualized therapy on top of PD-1 blockade — and the INT modality gains randomized Phase 3 validation with read-through to the sibling INTerpath programs (NSCLC, bladder, 1L melanoma). Physicians on this page flag the open questions: magnitude of benefit, durability, OS, manufacturing turnaround and cost.
Source: Merck/Moderna topline PRINTerpath-001 in the News
INTerpath-001 FAQ
What is the INTerpath-001 trial?
INTerpath-001 (NCT05933577, V940-001) is a randomized, double-blind, placebo- and active-comparator-controlled global Phase 3 trial of adjuvant intismeran autogene (V940 / mRNA-4157), an mRNA-based individualized neoantigen therapy jointly developed by Merck and Moderna, in combination with pembrolizumab (Keytruda) versus pembrolizumab alone in patients with completely resected, high-risk stage IIB-IV cutaneous melanoma. It enrolled 1,137 patients, randomized 2:1 to intismeran (1 mg every three weeks for up to nine doses) plus pembrolizumab (400 mg every six weeks for up to nine cycles, approximately one year) versus pembrolizumab alone.
What did INTerpath-001 show?
Per the August 19, 2026 topline announcement, the trial met both its primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS), with statistically significant and clinically meaningful improvements versus pembrolizumab alone. Numeric results have not been disclosed; data will be presented at an upcoming international medical meeting. The trial continues to evaluate other secondary endpoints including overall survival. Safety was consistent with previously reported studies of the combination, with no new safety signals.
What is intismeran autogene?
An mRNA-based individualized neoantigen therapy (INT): each patient's resected tumor is sequenced, up to 34 patient-specific neoantigens are encoded on a single mRNA, and the therapy is manufactured individually to train that patient's immune system to recognize and attack their cancer. It was formerly known as mRNA-4157 or V940.
How do these results relate to KEYNOTE-942?
KEYNOTE-942 was the randomized Phase 2b antecedent (n=157, resected stage III/IV melanoma). It showed a consistent RFS benefit at every analysis - primary (Nov 2022 cut): HR 0.561 (95% CI 0.309-1.017); 3-year: HR 0.510 (0.288-0.906); 5-year: HR 0.510 (0.294-0.887), with 5-year DMFS HR 0.411 (0.200-0.843) - per the ASCO 2026 presentation and the topline PR. Important: hazard-ratio figures circulating on announcement day are these KEYNOTE-942 Phase 2b numbers - INTerpath-001's own magnitude of benefit has not yet been disclosed.
Is intismeran autogene approved?
No. Intismeran autogene plus pembrolizumab is investigational and not approved by the FDA or any other regulator. Merck and Moderna stated they will engage with regulators on filing submissions based on INTerpath-001. This is the first positive Phase 3 trial for an individualized neoantigen therapy.