Non-small Cell Lung Cancer
Conditions
Brief summary
This is a phase 3, randomized, double-blind study of adjuvant MK-1084 plus subcutaneous pembrolizumab and berahyaluronidase alfa (MK-3475A) versus adjuvant placebo plus MK-3475a in participants with completely resected stage IIA-IIIB (N2), KRAS G12C-mutant non-small cell lung cancer following receipt of either neoadjuvant pembrolizumab plus chemotherapy or adjuvant chemotherapy. The primary goal of the study is to compare adjuvant MK-1084 plus MK-3475A to adjuvant placebo plus MK-3475A with respect to disease-free survival (DFS) as assessed by the investigator.
Interventions
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a histological/cytological diagnosis of non-small cell lung cancer (NSCLC) with predominantly nonsquamous histology and meets one of the following criteria: * Has newly diagnosed, treatment-naïve, resectable, clinical Stage IIA-IIIB (N2) NSCLC * Has completely resected, pathological Stage IIA-IIIB (N2) NSCLC, including those previously treated outside the study with neoadjuvant platinum-doublet chemotherapy plus pembrolizumab or MK-3475A, or those who received adjuvant platinum-doublet chemotherapy. * Tumor tissue shows the presence of Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation * No more than 12 weeks have elapsed between either the surgery following neoadjuvant treatment or last dose of adjuvant platinum-based chemotherapy and the first dose of investigational adjuvant study intervention. * Has no evidence of disease based on postsurgical radiological assessment as documented by contrast-enhanced chest/abdomen computed tomography (or magnetic resonance imaging) within 28 days before randomization * Has an Eastern Cooperative Oncology Group performance status of 0 or 1 within 10 days before the first dose of the study intervention * Human immunodeficiency virus-infected participants must have well controlled HIV on antiretroviral therapy * Participants who are Hepatitis B surface antigen positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
Exclusion criteria
* Has a diagnosis of any 1 of the following tumor types/locations: small cell lung cancer or, for mixed tumors, presence of small cell elements, neuroendocrine tumor with large cell components, sarcomatoid carcinoma, or NSCLC involving the superior sulcus * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, chronic diarrhea) * Has uncontrolled, significant cardiovascular disease or cerebrovascular disease within the 6 months preceding study intervention * Is unable to swallow orally administered medication, or has a gastrointestinal disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction, or malabsorption) * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Has an active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy * Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has active infection requiring systemic therapy * Has not adequately recovered from major surgery or has ongoing surgical complications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival (DFS) | Up to ~11 years | DFS is the time from randomization to any recurrence (local, locoregional, regional, or distant), occurrence of new primary NSCLC, or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Up to ~11 years | OS is the time from randomization to death due to any cause. |
| Distant Metastasis-Free Survival (DMFS) | Up to ~11 years | DMFS is the time from randomization to the first documented distant metastasis or death due to any cause, whichever occurs first. Distant metastasis refers to cancer that has spread from the original (primary) tumor to distant organs or distant lymph nodes. |
| Lung Cancer Specific Survival (LCSS) | Up to ~11 years | LCSS is the time from randomization to the date of 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 (Item 29) and Quality of Life (Item 30) Combined Score | Up to ~11 years | Change from baseline in Global health status/QoL score (QLQ-C30 Items 29 and 30). |
| Change from Baseline in the EORTC-QLQ-C30 Physical Functioning (Items 1-5) Combined Score | Up to ~11 years | Change from baseline in physical functioning score (QLQ-C30 Items 1 to 5). |
| Change from Baseline in the EORTC-QLQ-C30 Role Functioning (Items 6 and 7) Combined Score | Up to ~11 years | Change from baseline in role functioning score (QLQ-C30 Items 6 and 7). |
| Change from Baseline in the EORTC-QLQ-C30 Dyspnea (Item 8) Score | Up to ~11 years | Change from baseline in dyspnea (QLQ-C30 Item 8). |
| Change from Baseline in the EORTC-Quality of Life Questionnaire-Lung Cancer 24 (QLQ-LC24) Coughing (Items 31 and 52) Combined Score | Up to ~11 years | Change from baseline in coughing scores (EORTC QLQ-LC24 Items 31 and 52). |
| Change from Baseline in the EORTC-QLQ-LC24 Chest Pain (Item 40) Score | Up to ~11 years | Change from baseline in chest pain score (EORTC QLQ-LC24 Item 40). |
| Number of Participants Who Experience an Adverse Event (AE) | Up to ~13.5 years | Number of participants with ≥1 AE. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to ~13.5 years | Number of participants discontinuing from study therapy due to AE. |
Countries
Ukraine
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed