A Clinical Study of Intismeran Autogene (V940) and Pembrolizumab (MK-3475) in People With Melanoma (V940-012/INTerpath-012)

NCT06961006 | Recruiting Phase 2 FDA Drug

• 4 other identifiers: V940-012INTerpath-0122023-504923-20-00U1111-1290-3969
• Study Type: interventional
• Target: 160
• Locations: 12 countries
• Sites: 38

Brief Summary

Researchers want to learn if intismeran autogene with pembrolizumab can stop advanced melanoma from growing or spreading. Melanoma is a type of skin cancer. Advanced means the cancer has spread to other parts of the body and cannot be removed with surgery. A standard (or usual) treatment for advanced melanoma is immunotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. Intismeran autogene is a study treatment designed to help a person's immune system attack their specific cancer. Pembrolizumab is an immunotherapy. The goal of this study is to learn if people who receive intismeran autogene with pembrolizumab live longer without the cancer growing or spreading than people who receive placebo with pembrolizumab. A placebo looks like the study treatment but has no study treatment in it. Using a placebo helps researchers better understand the effects of a study treatment.

Conditions

Malignant Melanoma

Keywords

Programmed Cell Death-1 (PD1, PD-1); Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1); Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  PFS is defined as the time from randomization to the first documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by investigator assessment or death due to any cause, whichever occurs first. Progressive disease (PD) is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS per RECIST 1.1 as assessed by investigator will be presented.

  Up to approximately 36 months

Secondary Outcomes (5)

• Objective Response Rate (ORR)

  Up to approximately 6 years

• Duration of Response (DOR)

  Up to approximately 6 years

• Overall Survival (OS)

  Up to approximately 6 years

• Number of Participants With ≥1 Adverse Event (AE)

  Up to approximately 27 months

• Number of Participants Discontinuing From Study Therapy Due to AE

  Up to approximately 24 months

Study Arms (2)

Intismeran autogene + Pembrolizumab

EXPERIMENTAL

Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection every 3 weeks (q3w) for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via intravenous (IV) infusion every 6 weeks (q6w) for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.

Biological: Intismeran autogene; Biological: Pembrolizumab

Placebo + Pembrolizumab

ACTIVE COMPARATOR

Participants will receive placebo via IM injection q3w for up to 9 doses (up to approximately 27 weeks) plus 400 mg of pembrolizumab via IV infusion q6w for up to 17 doses, or for a total treatment duration of up to approximately 2 years, or until disease progression or discontinuation.

Biological: Pembrolizumab; Other: Placebo

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Intismeran autogene + Pembrolizumab; Placebo + Pembrolizumab

Placebo OTHER

IM injection

Placebo + Pembrolizumab

Intismeran autogene BIOLOGICAL

IM injection

Also known as: mRNA-4157, V940

Intismeran autogene + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (38)

Highlands Oncology Group ( Site 4042)

Springdale, Arkansas, 72762, United States

RECRUITING

UCSF Medical Center at Mission Bay ( Site 4044)

San Francisco, California, 94158, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center ( Site 4047)

Hackensack, New Jersey, 07601, United States

RECRUITING

Inova Schar Cancer Institute ( Site 4046)

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center ( Site 4041)

Seattle, Washington, 98109, United States

RECRUITING

Blacktown Hospital ( Site 2001)

Blacktown, New South Wales, 2148, Australia

RECRUITING

Melanoma Institute Australia ( Site 2000)

Wollstonecraft, New South Wales, 2065, Australia

RECRUITING

One Clinical Research ( Site 2002)

Nedlands, Western Australia, 6009, Australia

RECRUITING

William Osler Health System (Brampton Civic Hospital) ( Site 2023)

Brampton, Ontario, L6R 3J7, Canada

RECRUITING

Sunnybrook Research Institute ( Site 2022)

Toronto, Ontario, M4N 3M5, Canada

RECRUITING

Centre Hospitalier Universitaire de Nice - Hôpital l'Archet-Dermatology Department ( Site 2042)

Nice, Alpes-Maritimes, 06202, France

RECRUITING

Hôpital Saint-Louis ( Site 2041)

Paris, Île-de-France Region, 75010, France

RECRUITING

Gustave Roussy ( Site 2040)

Villejuif, Île-de-France Region, 94800, France

RECRUITING

NCT ( Site 2065)

Heidelberg, Baden-Wurttemberg, 69120, Germany

RECRUITING

Universitätsklinikum Frankfurt Goethe-Universität ( Site 2063)

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

Universitaetsklinikum Koeln ( Site 2064)

Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

Universitaetsklinikum Essen ( Site 2061)

Essen, North Rhine-Westphalia, 45147, Germany

RECRUITING

Universitaetsklinikum Hamburg-Eppendorf ( Site 2060)

Hamburg, 20251, Germany

RECRUITING

General Hospital of Athens "Laiko" ( Site 2080)

Athens, Attica, 115 27, Greece

RECRUITING

Metropolitan Hospital ( Site 2082)

Athens, Attica, 18547, Greece

RECRUITING

European Interbalkan Medical Center ( Site 2081)

Thessaloniki, 570 01, Greece

RECRUITING

HaEmek Medical Center ( Site 3003)

Afula, 1834111, Israel

RECRUITING

Hadassah Medical Center ( Site 3001)

Jerusalem, 9112001, Israel

RECRUITING

Rabin Medical Center ( Site 3002)

Petah Tikva, 4941492, Israel

RECRUITING

Sheba Medical Center ( Site 3000)

Ramat Gan, 5265601, Israel

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano ( Site 3021)

Milan, Milano, 20133, Italy

RECRUITING

Istituto Nazionale Tumori IRCCS Fondazione Pascale ( Site 3020)

Naples, 80131, Italy

RECRUITING

Istituto Oncologico Veneto IRCCS ( Site 3022)

Padova, 35128, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 3023)

Roma, 00168, Italy

RECRUITING

Harbour Cancer & Wellness ( Site 3040)

Auckland, 1023, New Zealand

RECRUITING

Uniwersytecki Szpital Kliniczny w Poznaniu ( Site 3061)

Poznan, Greater Poland Voivodeship, 50 659, Poland

RECRUITING

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie ( Site 3060)

Warsaw, Masovian Voivodeship, 02-781, Poland

RECRUITING

Unidade Local de Saude Lisboa Ocidental - Hospital de São Francisco Xavier ( Site 4002)

Lisbon, Lisbon District, 1449-005, Portugal

RECRUITING

Unidade Local de Saude de Santa Maria - Hospital de Santa Maria ( Site 4001)

Lisbon, 1649-035, Portugal

RECRUITING

Instituto Português de Oncologia do Porto Francisco Gentil, EPE ( Site 4000)

Porto, 4200-072, Portugal

RECRUITING

Hospital Universitari Vall d'Hebron ( Site 3081)

Barcelona, 08035, Spain

RECRUITING

Hospital Clínic Barcelona ( Site 3080)

Barcelona, 08036, Spain

RECRUITING

Hospital Universitario Ramón y Cajal-Medical Oncology ( Site 3082)

Madrid, 28034, Spain

RECRUITING

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Melanoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2025
• First Posted: May 7, 2025
• Study Start: May 29, 2025
• Primary Completion (Estimated): July 22, 2028
• Study Completion (Estimated): September 5, 2031
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

AU (3); FR (3); IT (4); US (5); PT (3); GR (3); PL (2); NZ (1); CA (2); ES (3); IL (4); DE (5)