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

Phase 3

Recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Biological: Intismeran autogene; Biological: Pembrolizumab; Other: Placebo

• Registration Number: NCT06077760
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-05
• Study First Submitted QC: 2023-10-05
• Study First Posted: 2023-10-11
• Study Start: 2023-12-06
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-16
• Last Update Posted: 2025-07-17
• Primary Completion: 2030-06-25
• Study Completion: 2035-12-21

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 868

Inclusion Criteria

The main inclusion criteria include but are not limited to the following:

• Has undergone margin negative, completely resected non-small cell lung cancer (NSCLC), and has pathological Stage II, IIIA, IIIB (N2) squamous or nonsquamous tumor, node, metastasis (TNM) staging per American Joint Committee on Cancer (AJCC) Eighth Edition guidelines.
• Has no evidence of disease before randomization.
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intismeran autogene + Pembrolizumab	Intismeran autogene	Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection once every 3 weeks for 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.
Placebo + Pembrolizumab	Pembrolizumab	Participants will receive intismeran autogene-matched placebo via IM injection once every 3 weeks for 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.
Placebo + Pembrolizumab	Placebo	Participants will receive intismeran autogene-matched placebo via IM injection once every 3 weeks for 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.
Intismeran autogene + Pembrolizumab	Pembrolizumab	Participants will receive 1 mg of intismeran autogene via intramuscular (IM) injection once every 3 weeks for 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.

Primary Outcome Measures

Name	Time	Method
Disease- Free Survival (DFS)	Up to ~78 months	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

Name	Time	Method
Distant Metastasis-Free Survival (DMFS)	Up to ~12 years	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.
Overall Survival (OS)	Up to ~12 years	OS is defined as the time from randomization to death due to any cause.
Number of Participants Who Experience an Adverse Event (AE)	Up to ~15 months	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.
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	Baseline and up to ~12 years	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 Dyspnea (Item 8) Score on the EORTC QLQ-C30	Baseline and up to ~12 years	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-C30 Physical Functioning (Items 1-5) Combined Score on the EORTC QLQ-C30	Baseline and up to ~12 years	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	Baseline and up to ~12 years	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-LC24 Chest Pain (Item 40) Score on the EORTC QLQ-LC24	Baseline and up to ~12 years	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 Discontinue Study Treatment Due to an AE	Up to ~12 months	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.
Change from Baseline in the EORTC QLQ-Lung Cancer Questionnaire (LC24) Coughing (Items 31 and 52) Combined Score on the EORTC QLQ-LC24	Baseline and up to ~12 years	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.
Lung Cancer Specific Survival (LCSS)	Up to ~12 years	LCSS is defined as the time from randomization to death due to lung cancer.

Trial Locations

Locations (195)

Alaska Oncology and Hematology ( Site 0039); 🇺🇸 Anchorage, Alaska, United States

The University of Arizona Cancer Center - North Campus ( Site 0071); 🇺🇸 Tucson, Arizona, United States

YUMA REGIONAL MEDICAL CENTER CANCER CENTER ( Site 0020); 🇺🇸 Yuma, Arizona, United States

UCLA Clinical & Translational Research Center (CTRC) ( Site 0059); 🇺🇸 Los Angeles, California, United States

St. Joseph Hospital-The Center for Cancer Prevention and Treatment ( Site 0074); 🇺🇸 Orange, California, United States

University of California, Irvine (UCI) Health - UC Irvine Medical Center ( Site 0030); 🇺🇸 Orange, California, United States

UCHealth Memorial Hospital-Heme Onc ( Site 0052); 🇺🇸 Colorado Springs, Colorado, United States

Mid Florida Hematology and Oncology Center ( Site 0014); 🇺🇸 Orange City, Florida, United States

AdventHealth Orlando-AdventHealth Medical Group Hematology & Oncology at Orlandoc ( Site 0013); 🇺🇸 Orlando, Florida, United States

Moffitt Cancer Center ( Site 0078); 🇺🇸 Tampa, Florida, United States

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