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RecruitingInterventionalPhase 3

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)

NCT ID: NCT07513376Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-12

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.

Arms & interventions

  • BiologicalIntismeran

    IM injection

  • BiologicalPembrolizumab coformulated with berahyaluronidase alfa

    SC injection

  • OtherPlacebo

    IM injection

Outcome measures

Primary

  • 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.

    Time frame: Up to approximately 98 months

Secondary

  • DFS as Assessed by BICR

    Time frame: Up to approximately 98 months

  • Distant Metastasis-Free Survival (DMFS)

    Time frame: Up to approximately 111 months

  • Overall Survival (OS)

    Time frame: Up to approximately 123 months

  • Number Participants Who Experience an Adverse Events (AE)

    Time frame: Up to approximately 144 months

  • Number of Participants Who Discontinue Study Treatment Due to an AE

    Time frame: 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

    Time frame: Baseline and up to approximately 36 months

  • Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score

    Time frame: Baseline and up to approximately 36 months

  • Change From Baseline in Role Functioning (EORTC QLQ-C30 Items 6-7) Score

    Time frame: Baseline and up to approximately 36 months

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (5)

Billings Clinic ( Site 3255)

Billings, Montana, 59101

Recruiting
Study Coordinator · Contact

NHO Revive Research Institute, LLC ( Site 3218)

Lincoln, Nebraska, 68506

Recruiting
Study Coordinator · Contact

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

Reno, Nevada, 89502

Recruiting
Study Coordinator · Contact

Altru Health System ( Site 3254)

Grand Forks, North Dakota, 58201

Recruiting
Study Coordinator · Contact

The University of Tennessee Medical Center ( Site 3223)

Knoxville, Tennessee, 37920

Recruiting
Study Coordinator · Contact