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Intismeran autogene (V940) plus pembrolizumab for advanced melanoma

A Phase 2, Randomized, Double-Blind, Placebo- and Active-Comparator-Controlled Clinical Study of V940 (mRNA-4157) Plus Pembrolizumab Versus Placebo Plus Pembrolizumab in Participants With First-Line Advanced Melanoma (INTerpath-012)

PHASE2 · Merck Sharp & Dohme LLC · NCT06961006

This trial will test whether adding intismeran autogene (V940) to pembrolizumab helps people with advanced melanoma live longer without the cancer growing or spreading.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment160 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC (industry)
Drugs / interventionsimmunotherapy, radiation, pembrolizumab
Locations38 sites (Springdale, Arkansas and 37 other locations)
Trial IDNCT06961006 on ClinicalTrials.gov

What this trial studies

This is a randomized, placebo-controlled Phase 2 trial comparing intismeran autogene plus pembrolizumab versus placebo plus pembrolizumab in adults with unresectable Stage III or IV cutaneous melanoma. Participants must have at least one measurable lesion and documented BRAF V600 status; some prior adjuvant or neoadjuvant therapy is allowed if relapse occurred more than 12 months after stopping treatment. Pembrolizumab is given as the standard PD-1 inhibitor while intismeran autogene is administered to prime the immune system against the tumor, with a matching placebo used in the control arm. The primary outcome is progression-free survival, with safety, response rate, and overall survival evaluated as additional endpoints.

Who should consider this trial

Good fit: Adults with unresectable Stage III or IV cutaneous melanoma who are treatment-naive for metastatic disease (or had prior adjuvant/neoadjuvant therapy with relapse >12 months after stopping), have documented BRAF status, and at least one measurable lesion are the intended candidates.

Not a fit: Patients with resectable disease, those who relapsed within 12 months of prior adjuvant therapy, or people with non-cutaneous melanoma subtypes are unlikely to be eligible or derive benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could extend the time patients with advanced melanoma live without disease progression compared with pembrolizumab alone.

How similar studies have performed: Other trials combining tumor-directed vaccines or immune-priming agents with PD-1 inhibitors in melanoma have shown promising signals but remain preliminary and not yet definitive.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

* Has unresectable and histologically confirmed Stage III or IV cutaneous melanoma per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
* Has been untreated for melanoma except if participant received prior adjuvant or neoadjuvant therapy with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein \[CTLA-4\], anti-programmed cell death 1 protein \[PD-1\] therapy or interferon), and only if relapse did not occur within 12 months after treatment discontinuation.
* Have documentation of serine/threonine-protein kinase B-raf (BRAF) V600-activating mutation status or had BRAF V600 mutation testing per local institutional standards during the screening period (participants with BRAF mutation positive melanoma as well as BRAF wild-type or unknown are eligible).
* Have the presence of at least 1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by the local site investigator/radiology assessment.
* Provides tumor tissue (preferably from a metastatic site and, if not available, from the primary tumor) that is suitable for next generation sequencing and biomarker analysis as required for this study.
* Participants with human immunodeficiency virus (HIV) must have well controlled HIV on antiretroviral therapy (ART).
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load prior to randomization.
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

* Has clinically significant heart failure, defined as New York Heart Association class III or IV, within the past 6 months, unless the disease is well controlled in the opinion of the investigator.
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease.
* Has ocular or mucosal melanoma.
* Received transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony-stimulating factor, granulocyte macrophage colony-stimulating factor, or recombinant erythropoietin) within 2 weeks of the Screening blood sample (including the blood sample for V940 generation).
* Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, lymphocyte activation gene 3 \[LAG-3\], tumor necrosis factor receptors \[OX-40 or CD137\]), with some exceptions.
* Received prior systemic anticancer therapy for melanoma before randomization, with some exceptions.
* Received prior radiotherapy within 2 weeks of start of study intervention or has ongoing radiation related toxicities.
* Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Received prior treatment with another universal or personalized cancer vaccine.

Where this trial is running

Springdale, Arkansas and 37 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Malignant Melanoma, Programmed Cell Death-1, Programmed Cell Death 1 Ligand 1, Programmed Cell Death 1 Ligand 2

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.