Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2), Individualized neoantigen therapy (INT)
Brief summary
The goal of this study is to learn if people who receive intismeran autogene and pembrolizumab after surgery are cancer-free longer than people who receive placebo and pembrolizumab. Researchers want to know if giving intismeran autogene and pembrolizumab after surgery can help prevent the cancer from coming back in people with non-small cell lung cancer (NSCLC) whose tumors did not respond completely to treatment before surgery (neoadjuvant treatment).
Interventions
BIOLOGICALPembrolizumab
IV Infusion
DRUGCisplatin
IV infusion
DRUGCarboplatin
IV infusion
DRUGPemetrexed
IV infusion
DRUGGemcitabine
IV infusion
DRUGPaclitaxel
IV infusion
BIOLOGICALIntismeran autogene
IM injection
OTHERPlacebo
IM injection
Sponsors
Merck Sharp & Dohme LLC
ModernaTX, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has histologically/cytologically confirmed diagnosis of previously untreated and pathologically confirmed resectable clinical Stage II, IIIA, or IIIB (N2) non-small cell lung cancer (NSCLC) \[American Joint Committee on Cancer (AJCC) 8th Edition\] * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study intervention * Participants who have not achieved a pathological complete response (pCR) following completion of neoadjuvant chemotherapy and pembrolizumab followed by surgery will be eligible * Confirmation that epidermal growth factor receptor (EGFR)-directed therapy is not indicated as primary therapy (documentation of absence of tumor-activating EGFR mutations \[eg, DEL19 or L858R\]) * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on anti-retroviral 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS) | Up to ~97 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
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to ~129 months | OS is defined as the time from randomization to death due to any cause. |
| Distant Metastasis-Free Survival (DMFS) | Up to ~129 months | 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. Distant metastasis refers to cancer that has spread from the original (primary) tumor and beyond local tissues and lymph nodes to distant organs or distant lymph nodes. |
| Disease-Free Survival 2 (DFS2) | Up to ~129 months | DFS2 is defined as the time from randomization to subsequent recurrence or disease progression after initiation of next-line anticancer therapy as assessed by the investigator, or death due to any cause, whichever occurs first. |
| Lung Cancer Specific Survival (LCSS) | Up to ~129 months | LCSS is defined as the time from randomization to death due to lung cancer specifically as assessed by the investigator. |
| 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) | Baseline and up to ~129 months | 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) | Baseline and up to ~129 months | 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) | Baseline and up to ~129 months | 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). Higher scores indicate a worse level of role functioning. Change from baseline in the role functioning (EORTC QLQ-C30 Items 6 and 7) combined score will be presented. |
| Number of participants with ≥1 adverse event (AE) | Up to ~129 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. |
| Number of participants discontinuing from study therapy due to AE(s) | Up to ~129 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. |
Countries
Argentina, Australia, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Japan, Netherlands, New Zealand, Peru, Poland, Romania, Singapore, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed