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A Study of V940 Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Non-small Cell Lung Cancer (V940-002)

Primary Purpose

Non-small Cell Lung Cancer

Status
Not yet recruiting
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
V940
Pembrolizumab
Placebo
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: Has surgically resected and histologically confirmed diagnosis of Stage II, IIIA, IIIB (N2) squamous or nonsquamous NSCLC as per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines. Has no evidence of disease at the time of providing documented consent for the main study. Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy. No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab. 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. 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: Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large cell components or a sarcomatoid carcinoma. HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. Received prior neoadjuvant therapy for their current NSCLC diagnosis. Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis. Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-PD-ligand 1 (L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor. Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication. Known additional malignancy that is progressing or has required active treatment within the past 5 years. Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Active infection requiring systemic therapy.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    V940 + Pembrolizumab

    Placebo + Pembrolizumab

    Arm Description

    Participants will receive 1 mg of V940 via intramuscular (IM) injection once every 3 weeks for up to 9 doses PLUS 400 mg of pembrolizumab via intravenous (IV) infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.

    Participants will receive V940-matched placebo via IM injection once every 3 weeks for up to 9 doses PLUS 400 mg of pembrolizumab via IV infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.

    Outcomes

    Primary Outcome Measures

    Disease- Free Survival (DFS)
    DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first.

    Secondary Outcome Measures

    Overall Survival (OS)
    OS is defined as the time from randomization to death due to any cause.
    Distant Metastasis-Free Survival (DMFS)
    DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis as assessed by the investigator, or death due to any cause, whichever occurs first.
    Lung Cancer Specific Survival (LCSS)
    LCSS is defined as the time from randomization to death due to lung cancer.
    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
    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. The change from baseline in global health status/quality of life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.
    Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
    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 worse 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
    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). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate 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.
    Change from Baseline in the EORTC QLQ-C30 Dyspnea (Item 8) Score on the EORTC QLQ-C30
    The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" 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 worse level of dyspnea. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented.
    Change from Baseline in the EORTC QLQ-Lung Cancer Questionnaire (LC24) Coughing (Items 31 and 52) Combined Score on the EORTC QLQ-LC24
    The EORTC QLQ-LC24 is a lung cancer specific health-related quality of life questionnaire. Participant responses to questions about coughing 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 more coughing. The change from baseline in coughing (EORTC QLQ-LC24 Items 31 and 52) combined score will be presented.
    Change from Baseline in the EORTC QLQ-LC24 Chest Pain (Item 40) Score on the EORTC QLQ-LC24
    The EORTC QLQ-LC24 is a lung cancer specific health-related quality of life questionnaire. Participant responses to the question "Have you had pain in your chest?" 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 more chest pain. The change from baseline in chest pain (EORTC QLQ-LC24 Item 40) score will be presented.
    Number of Participants Who Experience an Adverse Event (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.
    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.

    Full Information

    First Posted
    October 5, 2023
    Last Updated
    October 18, 2023
    Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    ModernaTX, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06077760
    Brief Title
    A Study of V940 Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Non-small Cell Lung Cancer (V940-002)
    Official Title
    A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Clinical Study of Adjuvant V940 (mRNA-4157) Plus Pembrolizumab Versus Adjuvant Placebo Plus Pembrolizumab in Participants With Resected Stage II, IIIA, IIIB (N2) Non-small Cell Lung Cancer
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 23, 2023 (Anticipated)
    Primary Completion Date
    June 25, 2030 (Anticipated)
    Study Completion Date
    December 21, 2035 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC
    Collaborators
    ModernaTX, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The goal of this study is to evaluate V940 plus pembrolizumab versus placebo plus pembrolizumab for the adjuvant treatment of completely resected (R0) Stage II, IIIA, IIIB (with nodal involvement [N2]) non-small cell lung cancer (NSCLC). The primary hypothesis is that V940 plus pembrolizumab is superior to placebo plus pembrolizumab with respect to disease-free survival (DFS) as assessed by the investigator.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non-small Cell Lung Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantInvestigator
    Allocation
    Randomized
    Enrollment
    868 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    V940 + Pembrolizumab
    Arm Type
    Experimental
    Arm Description
    Participants will receive 1 mg of V940 via intramuscular (IM) injection once every 3 weeks for up to 9 doses PLUS 400 mg of pembrolizumab via intravenous (IV) infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.
    Arm Title
    Placebo + Pembrolizumab
    Arm Type
    Active Comparator
    Arm Description
    Participants will receive V940-matched placebo via IM injection once every 3 weeks for up to 9 doses PLUS 400 mg of pembrolizumab via IV infusion once every 6 weeks for up to 9 doses until disease recurrence or unacceptable toxicity or for a total treatment duration of up to approximately 1 year, whichever is sooner.
    Intervention Type
    Biological
    Intervention Name(s)
    V940
    Other Intervention Name(s)
    mRNA-4157
    Intervention Description
    IM injection
    Intervention Type
    Biological
    Intervention Name(s)
    Pembrolizumab
    Other Intervention Name(s)
    MK-3475, KEYTRUDA®
    Intervention Description
    IV infusion
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    IM injection
    Primary Outcome Measure Information:
    Title
    Disease- Free Survival (DFS)
    Description
    DFS is defined as the time from randomization to any recurrence (local, locoregional, regional or distant), occurrence of new primary NSCLC, as assessed by the investigator, or death due to any cause, whichever occurs first.
    Time Frame
    Up to ~78 months
    Secondary Outcome Measure Information:
    Title
    Overall Survival (OS)
    Description
    OS is defined as the time from randomization to death due to any cause.
    Time Frame
    Up to ~12 years
    Title
    Distant Metastasis-Free Survival (DMFS)
    Description
    DMFS is defined as the time from randomization to the first diagnosis of a distant metastasis as assessed by the investigator, or death due to any cause, whichever occurs first.
    Time Frame
    Up to ~12 years
    Title
    Lung Cancer Specific Survival (LCSS)
    Description
    LCSS is defined as the time from randomization to death due to lung cancer.
    Time Frame
    Up to ~12 years
    Title
    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
    Description
    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. The change from baseline in global health status/quality of life (EORTC QLQ-C30 Items 29 and 30) combined score will be presented.
    Time Frame
    Baseline and up to ~12 years
    Title
    Change from Baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30
    Description
    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 worse level of physical functioning. The change from baseline in physical functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented.
    Time Frame
    Baseline and up to ~12 years
    Title
    Change from Baseline in the EORTC QLQ-C30 Role Functioning (Items 6 and 7) Combined Score on the EORTC QLQ-C30
    Description
    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). Using linear transformation, raw scores will be standardized, so that scores range from 0 to 100. Higher scores indicate 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.
    Time Frame
    Baseline and up to ~12 years
    Title
    Change from Baseline in the EORTC QLQ-C30 Dyspnea (Item 8) Score on the EORTC QLQ-C30
    Description
    The EORTC QLQ-C30 is a 30-item questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" 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 worse level of dyspnea. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score will be presented.
    Time Frame
    Baseline and up to ~12 years
    Title
    Change from Baseline in the EORTC QLQ-Lung Cancer Questionnaire (LC24) Coughing (Items 31 and 52) Combined Score on the EORTC QLQ-LC24
    Description
    The EORTC QLQ-LC24 is a lung cancer specific health-related quality of life questionnaire. Participant responses to questions about coughing 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 more coughing. The change from baseline in coughing (EORTC QLQ-LC24 Items 31 and 52) combined score will be presented.
    Time Frame
    Baseline and up to ~12 years
    Title
    Change from Baseline in the EORTC QLQ-LC24 Chest Pain (Item 40) Score on the EORTC QLQ-LC24
    Description
    The EORTC QLQ-LC24 is a lung cancer specific health-related quality of life questionnaire. Participant responses to the question "Have you had pain in your chest?" 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 more chest pain. The change from baseline in chest pain (EORTC QLQ-LC24 Item 40) score will be presented.
    Time Frame
    Baseline and up to ~12 years
    Title
    Number of Participants Who Experience an Adverse Event (AE)
    Description
    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.
    Time Frame
    Up to ~15 months
    Title
    Number of Participants Who Discontinue Study Treatment Due to an AE
    Description
    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.
    Time Frame
    Up to ~12 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: The main inclusion criteria include but are not limited to the following: Has surgically resected and histologically confirmed diagnosis of Stage II, IIIA, IIIB (N2) squamous or nonsquamous NSCLC as per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines. Has no evidence of disease at the time of providing documented consent for the main study. Has received at least one dose of adjuvant treatment with standard of care platinum doublet chemotherapy. No more than 24 weeks have elapsed between surgical resection of curative intent and the first dose of pembrolizumab. 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. 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: Diagnosis of small cell lung cancer (SCLC) or, for mixed tumors, presence of small cell elements, or has a neuroendocrine tumor with large cell components or a sarcomatoid carcinoma. HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. Received prior neoadjuvant therapy for their current NSCLC diagnosis. Received or is a candidate to receive radiotherapy for their current NSCLC diagnosis. Received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-PD-ligand 1 (L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor. Received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study medication. Known additional malignancy that is progressing or has required active treatment within the past 5 years. Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Active infection requiring systemic therapy.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Links:
    URL
    http://www.merckclinicaltrials.com
    Description
    Merck Clinical Trials Information
    URL
    https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=V940-002&&kw=V940-002
    Description
    Plain Language Summary

    Learn more about this trial

    A Study of V940 Plus Pembrolizumab (MK-3475) Versus Placebo Plus Pembrolizumab in Participants With Non-small Cell Lung Cancer (V940-002)

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