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) (INTerpath-014)

A Phase 3, Randomized, Placebo-Controlled Study of Adjuvant Intismeran Autogene Plus Subcutaneous Pembrolizumab and Berahyaluronidase Alfa (MK-3475A) or Intismeran Autogene Monotherapy Versus Placebo in Participants With Completely Resected High-Risk Stage I Non-Small Cell Lung Cancer (INTerpath-014)

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.

Study Overview

• Status: Recruiting
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Other: Placebo; Biological: Intismeran; Biological: Pembrolizumab coformulated with berahyaluronidase alfa

• Study Type: Interventional
• Enrollment (Estimated): 876
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Toll Free Number; Phone Number: 1-888-577-8839; Email: Trialsites@msd.com

Study Locations

• Australia
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • One Clinical Research ( Site 0501)
      • Contact: Study Coordinator; Phone Number: +61410565868
• Canada
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Recruiting
      • Kingston Health Sciences Centre-Kingston General Hospital Site ( Site 2503)
      • Contact: Study Coordinator; Phone Number: 6135496666
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • Recruiting
      • Centre Hospitalier de l'Université de Montréal ( Site 2501)
      • Contact: Study Coordinator; Phone Number: 5148908000x26832
• Taiwan
  • Tainan, Taiwan, 704
    • Recruiting
    • National Cheng Kung University Hospital ( Site 5300)
    • Contact: Study Coordinator; Phone Number: +88662353535
• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Recruiting
      • NHO Revive Research Institute, LLC ( Site 3218)
      • Contact: Study Coordinator; Phone Number: 402-484-4900
  • Nevada
    • Reno, Nevada, United States, 89502
      • Recruiting
      • Renown Regional Medical Center-Renown Health Medical Oncology ( Site 3207)
      • Contact: Study Coordinator; Phone Number: 775-982-4000
  • North Dakota
    • Grand Forks, North Dakota, United States, 58201
      • Recruiting
      • Altru Health System ( Site 3254)
      • Contact: Study Coordinator; Phone Number: 701-780-5400

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Intismeran + Pembrolizumab with Berahyaluronidase Alfa; Participants will receive intismeran 1 mg via intramuscular (IM) injection plus pembrolizumab coformulated with berahyaluronidase alfa 790 mg via subcutaneous (SC) injection.	Biological: Intismeran; IM injection; Other Names: mRNA-4157; V940; Biological: Pembrolizumab coformulated with berahyaluronidase alfa; SC injection; Other Names: MK-3475A
Experimental: Arm B: Intismeran; Participants will receive intismeran 1 mg via IM injection.	Biological: Intismeran; IM injection; Other Names: mRNA-4157; V940
Placebo Comparator: Arm C: Placebo; Participants will receive dose-matched placebo via IM injection.	Other: Placebo; IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-Free Survival (DFS) as Assessed by Blinded Independent Central Review (BICR) in Participants With Nonsquamous Non-Small Cell Lung Cancer (NSCLC) in Arm A and Arm C	DFS is defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) by BICR, or death due to any cause, whichever occurs first.	Up to approximately 98 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DFS as Assessed by BICR	DFS is defined as the time from randomization to any recurrence (local, locoregional, regional, or distant) by BICR, or death due to any cause, whichever occurs first.	Up to approximately 98 months
Distant Metastasis-Free Survival (DMFS)	DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis by BICR or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes.	Up to approximately 111 months
Overall Survival (OS)	OS is defined as the time from randomization to death due to any cause.	Up to approximately 123 months
Number Participants Who Experience an Adverse Events (AE)	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who experience an AE will be reported.	Up to approximately 144 months
Number of Participants Who Discontinue Study Treatment Due to an AE	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants who discontinue study intervention due to an AE will be reported.	Up to approximately 144 months
Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score	EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in global health status/quality of life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.	Baseline and up to approximately 36 months
Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score will be presented.	Baseline and up to approximately 36 months
Change From Baseline in Role Functioning (EORTC QLQ-C30 Items 6-7) Score	EORTC QLQ-C30 is a questionnaire to assess the overall QoL 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). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. A higher score indicates a worse level of role functioning. The change from baseline in role functioning (EORTC QLQ-C30 Items 6 and 7) combined score will be presented.	Baseline and up to approximately 36 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: ModernaTX, Inc.
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2026
• Primary Completion (Estimated): August 22, 2034
• Study Completion (Estimated): May 11, 2038

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 7, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: V940-014 (Other Identifier: MSD); U1111-1323-9950 (Registry Identifier: UTN); 2025-522643-18-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No