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NCT07513376PHASE3Recruiting

A Clinical Trial of Adjuvant Intismeran (V940) With or Without Pembrolizumab Coformulated With Berahyaluronidase Alfa (MK-3475A) in High-Risk Stage I Non-Small Cell Lung Cancer (V940-014)

Merck Sharp & Dohme LLC

Start Date

5/4/2026

Completion Date

5/11/2038

Summary

Researchers are looking for new ways to treat high-risk, localized non-small cell lung cancer (NSCLC) that has been removed with surgery. People with high-risk, localized NSCLC are often treated with surgery. Researchers want to learn if participants can receive 1 or 2 trial treatments to help prevent NSCLC from coming back after surgery. One trial medicine is intismeran (also called V940/mRNA-4157) and the other is subcutaneous pembrolizumab (also called SC pembrolizumab and MK-3475A). Intismeran is designed to help a person's immune system attack their specific cancer. SC pembrolizumab is an immunotherapy treatment which helps the immune system fight cancer. The main purpose of this study is to evaluate whether adjuvant intismeran autogene (V940) in combination with SC pembrolizumab and berahyaluronidase alfa (MK-3475A) or intismeran monotherapy improves disease-free survival (DFS) compared with placebo in participants with completely resected high-risk Stage I NSCLC.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has a histological diagnosis of pathological Stage I (tumor ≤4 cm) non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) 9th Edition with at least 1of the following high-risk pathologic features as assessed locally: tumor size \>2cm, visceral pleural invasion, lymphovascular invasion, or high-grade histology * Has undergone a complete surgical resection of the primary NSCLC * Has not received other prior treatment outside of definitive surgery (including but not limited to chemotherapy, immunotherapy, targeted therapy, or radiotherapy) for their current Stage I NSCLC * Has provided a tissue sample from recent surgery along with the required blood sample * Human immunodeficiency virus (HIV)-infected participants 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 diagnosis of any 1 of the following: small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, neuroendocrine tumor with large cell components, sarcomatoid carcinoma, or two synchronous primary NSCLCs * Has any clinically significant cardiovascular disease within 12 months before randomization, including a history of coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), valvular heart disease requiring surgical intervention, New York Heart Association Class III-IV heart failure, unstable angina, myocardial infarction (MI), pulmonary hypertension, cardiovascular accident (CVA), or hemodynamically unstable cardiac arrhythmia * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Has active autoimmune disease that has required systemic treatment in the past 2 years. Hormonal supplementation (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed * Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has active infection requiring systemic therapy other than those permitted in protocol * Has history of stem cell/solid organ transplant * Participants who have not adequately recovered from major surgery or have ongoing surgical complications

Interventions

BIOLOGICAL

Intismeran

BIOLOGICAL

Pembrolizumab coformulated with berahyaluronidase alfa

OTHER

Placebo

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Conditions

Non-small Cell Lung Cancer

Locations

Smilow Cancer Center at Yale-New Haven ( Site 3253)

New Haven, Connecticut 06511

United States

Billings Clinic ( Site 3255)

Billings, Montana 59101

United States

NHO Revive Research Institute, LLC ( Site 3218)

Lincoln, Nebraska 68506

United States

Renown Regional Medical Center-Renown Health Medical Oncology ( Site 3207)

Reno, Nevada 89502

United States

White Plains Hospital ( Site 3213)

White Plains, New York 10601

United States

WakeMed Raleigh Campus ( Site 3214)

Raleigh, North Carolina 27610

United States

Altru Health System ( Site 3254)

Grand Forks, North Dakota 58201

United States

The University of Tennessee Medical Center ( Site 3223)

Knoxville, Tennessee 37920

United States

West Virginia University ( Site 3237)

Morgantown, West Virginia 26506

United States

Royal North Shore Hospital ( Site 0502)

St Leonards, New South Wales 2065

Australia

One Clinical Research ( Site 0501)

Nedlands, Western Australia 6009

Australia

Hamilton Health Sciences-Juravinski Cancer Centre ( Site 2506)

Hamilton, Ontario L8V 5C2

Canada

Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 2503)

Kingston, Ontario K7L 2V7

Canada

Centre Hospitalier de l'Université de Montréal ( Site 2501)

Montreal, Quebec H2X 3E4

Canada

Augusta-Kranken-Anstalt ( Site 2702)

Bochum, North Rhine-Westphalia 44791

Germany

Errikos Dunant Hospital Center ( Site 5004)

Athens, Attica 115 26

Greece

European Interbalkan Medical Center-Oncology Department ( Site 5000)

Thessaloniki, 570 01

Greece

Pecsi Tudomanyegyetem Klinikai Kozpont ( Site 4401)

Pécs, Baranya 7623

Hungary

Borsod-Abaúj-Zemplén Vármegyei Központi Kórház És Egyetemi Oktatókórház ( Site 4409)

Miskolc, Borsod-Abauj Zemplen county 3526

Hungary

Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 4406)

Kecskemét, Bács-Kiskun county 6000

Hungary

Országos Onkológiai Intézet ( Site 4405)

Budapest, 1122

Hungary

Rambam Health Care Campus ( Site 3303)

Haifa, 3109601

Israel

Shaare Zedek Medical Center ( Site 3301)

Jerusalem, 9103102

Israel

Hadassah Medical Center ( Site 3305)

Jerusalem, 9112001

Israel

Meir medical center ( Site 3306)

Kfar Saba, 4428164

Israel

Sheba Medical Center ( Site 3302)

Ramat Gan, 5265601

Israel

Azienda Ospedaliero Universitaria Maggiore della Carità ( Site 2803)

Novara, 28100

Italy

Ziekenhuis St. Jansdal ( Site 4800)

Harderwijk, Gelderland 3844 DG

Netherlands

Radboudumc ( Site 4806)

Nijmegen, Gelderland 6525 GA

Netherlands

Frisius Medisch Centrum ( Site 4808)

Leeuwarden, Provincie Friesland 8934 AD

Netherlands

Meander Medisch Centrum ( Site 4802)

Amersfoort, Utrecht 3813 TZ

Netherlands

University Medical Center Groningen ( Site 4807)

Groningen, 9713 GZ

Netherlands

Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 4202)

Poznan, Greater Poland Voivodeship 60-569

Poland

IP Clinic ( Site 4204)

Lodz, Łódź Voivodeship 90-752

Poland

Wojewodzki Szpital Specjalistyczny im. sw. Rafala w Czerwonej Gorze ( Site 4206)

Chęciny, Świętokrzyskie Voivodeship 26-060

Poland

Hospital de Cruces ( Site 0308)

Barakaldo, Bizkaia 48903

Spain

HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 0307)

Madrid, 28009

Spain

Hospital Clinico San Carlos ( Site 0303)

Madrid, 28040

Spain

Hospital Universitario Virgen Macarena ( Site 0306)

Seville, 41007

Spain

Chang Gung Memorial Hospital at Kaohsiung ( Site 5302)

Kaohsiung City, 83301

Taiwan

China Medical University Hospital ( Site 5303)

Taichung, 40447

Taiwan

Taichung Veterans General Hospital ( Site 5301)

Taichung, 407

Taiwan

National Cheng Kung University Hospital ( Site 5300)

Tainan, 704

Taiwan

Taipei Medical University Hospital ( Site 5305)

Taipei, 110

Taiwan

Hacettepe Universite Hastaneleri-oncology hospital ( Site 4300)

Ankara, 6230

Turkey (Türkiye)

İstinye Üniversitesi Liv Hospital-Topkapi ( Site 4307)

Istanbul, 34010

Turkey (Türkiye)