A Clinical Study of Intismeran Autogene (V940) Plus Pembrolizumab in People With High-Risk Melanoma (V940-001)

Phase 3

Active, not recruiting

• Conditions: Melanoma
• Interventions: Biological: Intismeran autogene; Biological: Pembrolizumab; Other: Placebo

• Registration Number: NCT05933577
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

The purpose of this study is to learn if intismeran autogene which is an individualized neoantigen therapy (INT; formerly, called messenger ribonucleic acid \[mRNA\]-4157) with pembrolizumab (MK-3475) is safe and prevents cancer from returning in people with high-risk melanoma. Researchers want to know if intismeran autogene with pembrolizumab is better than receiving pembrolizumab alone at preventing the cancer from returning.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-06-27
• Study First Submitted QC: 2023-06-27
• Study First Posted: 2023-07-06
• Study Start: 2023-07-19
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-22
• Last Update Posted: 2025-09-24
• Primary Completion: 2029-10-26
• Study Completion: 2030-09-26

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 1089

Inclusion Criteria

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

• Has surgically resected and histologically/pathologically confirmed diagnosis of Stage IIB or IIC, III, or IV cutaneous melanoma
• Has not received any prior systemic therapy for their melanoma beyond surgical resection
• No more than 13 weeks have passed between final surgical resection that rendered the participant disease-free and the first dose of pembrolizumab
• Is disease free at the time of providing documented consent for the study
• Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral therapy (ART)

Exclusion Criteria

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

• Has ocular or mucosal melanoma
• Has cancer that has spread to other parts of the body and cannot be removed with surgery
• Has heart failure within the past 6 months
• Has received prior cancer therapy or another cancer vaccine
• Has another known cancer that that has spread to other parts of the body or has required treatment within the past 3 years
• Has severe reaction to study medications or any of their substance used to prepare a drug
• Have not recovered from major surgery or have ongoing surgical complications

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intismeran autogene + Pembrolizumab	Intismeran autogene	Participants receive up to 9 doses of intismeran autogene via an intramuscular (IM) injection (every 3 weeks) plus up to 9 doses of pembrolizumab via an intravenous (IV) infusion (once every 6 weeks) until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner.
Intismeran autogene + Pembrolizumab	Pembrolizumab	Participants receive up to 9 doses of intismeran autogene via an intramuscular (IM) injection (every 3 weeks) plus up to 9 doses of pembrolizumab via an intravenous (IV) infusion (once every 6 weeks) until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner.
Placebo + Pembrolizumab	Pembrolizumab	Participants receive up to 9 doses of dose matched placebo to intismeran autogene via an IM injection (every 3 weeks) plus up to 9 doses of pembrolizumab via an IV infusion (once every 6 weeks) until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner.
Placebo + Pembrolizumab	Placebo	Participants receive up to 9 doses of dose matched placebo to intismeran autogene via an IM injection (every 3 weeks) plus up to 9 doses of pembrolizumab via an IV infusion (once every 6 weeks) until disease recurrence or unacceptable toxicity, or for a total treatment duration of up to approximately 56 weeks, whichever is sooner.

Primary Outcome Measures

Name	Time	Method
Recurrence-Free Survival (RFS)	Up to approximately 74 months	RFS is defined as the length of time from when the participant starts the study until either the cancer comes back, or the cancer spreads as assessed by the investigator, or death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Overall-Survival (OS)	Up to approximately 85 months	OS is the length of time that people are alive after joining the study.
Number of Participants Who Discontinue Study Treatment Due to an AE	Up to approximately 56 weeks	An AE is a health problem that happens or worsens during a study. Number of participants who discontinue study treatment will be reported.
Distant Metastasis-Free Survival (DMFS)	Up to approximately 85 months	DMFS is the length of time from when the participant starts the study until either the cancer spreads from where it started to other parts of the body as assessed by the investigator, or death due to any cause.
Number of Participants Who Experience an Adverse Event (AE)	Up to approximately 68 weeks	An AE is a health problem that happens or worsens during a study. Number of participants who experience an AE will be reported.
Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30	Baseline and up to approximately 85 months	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning will be scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better level of physical functioning. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.
Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30	Baseline and up to approximately 85 months	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "Were you limited in doing either your work or other daily activities during the past week?" and " Were you limited in pursuing your hobbies or other leisure time activities during the past week?" will be scored on a 4-point scale (1=Not at All to 4=Very Much). Higher scores indicate a more impaired level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6-7) combined score will be presented.
Change from Baseline in the European Organization for Research and Treatment of Cancer (EORTC)-Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status/Quality of Life (Items 29 and 30) Combined Score	Baseline and up to approximately 85 months	The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" will be scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate a better overall health status. Per protocol, the change from baseline in EORTC QLQ-C30 Items 29 and 30 combined score will be presented.

Trial Locations

Locations (165)

Columbia University Irving Medical Center-CUIMC Herbert Irving Comprehensive Cancer Center Clinical ( Site 1908); 🇺🇸 New York, New York, United States

Westmead Hospital ( Site 1001); 🇦🇺 Westmead, New South Wales, Australia

Centre Hospitalier de l'Université de Montréal-Unité de Recherche Clinique en Oncologie et Hématolo ( Site 1100); 🇨🇦 Montreal, Quebec, Canada

IMAT S.A.S ( Site 2503); 🇨🇴 Montería, Departamento de Córdoba, Colombia

Assistance Publique Hôpitaux de Marseille - Hôpital de la Ti-Service de Dermatologie et Cancérologi ( Site 1203); 🇫🇷 Marseille, Bouches-du-Rhone, France

Istituto Nazionale Tumori IRCCS Fondazione Pascale-s.c. melanoma, immunoterapia oncologica e terapi ( Site 1400); 🇮🇹 Napoli, Italy

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 2900); 🇵🇱 Warsaw, Masovian Voivodeship, Poland

Uniwersyteckie Centrum Kliniczne-Klinika Chirurgii Onkologicznej, Transplantacyjnej i Ogólnej ( Site 2906); 🇵🇱 Gdansk, Pomeranian Voivodeship, Poland

Swietokrzyskie Centrum Onkologii, Samodzielny Publiczny Zakl-Klinika Onkologii Klinicznej, Dzial Ch ( Site 2902); 🇵🇱 Kielce, Świętokrzyskie Voivodeship, Poland

HOSPITAL CLÍNIC DE BARCELONA-ICHMO- Clinic Institut of Haematological and Oncological diseases ( Site 1600); 🇪🇸 Barcelona, Catalonia, Spain

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