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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Non-small Cell Lung Cancer

Intervention / Treatment
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* Biological: V940
* Biological: Pembrolizumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V940 + Pembrolizumab<br>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. | Biological: V940<br>* IM injection<br>* Other names: mRNA-4157;Biological: Pembrolizumab<br>* IV infusion<br>* Other names: KEYTRUDA®;|
| Active Comparator: Placebo + Pembrolizumab<br>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. | Biological: Pembrolizumab<br>* IV infusion<br>* Other names: KEYTRUDA®;Other: Placebo<br>* IM injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Up to  78 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and up to  12 years | 
| 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. | Baseline and up to  12 years | 
| 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. | Baseline and up to  12 years | 
| 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. | Baseline and up to  12 years | 
| 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. | Baseline and up to  12 years | 
| 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. | Baseline and up to  12 years | 
| 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. | Up to  15 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. | Up to  12 months | 
| Overall Survival (OS) | OS is defined as the time from randomization to death due to any cause. | Up to  12 years | 
| 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. | Up to  12 years | 
| Lung Cancer Specific Survival (LCSS) | LCSS is defined as the time from randomization to death due to lung cancer. | Up to  12 years |