Malignant Neoplasm
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)
Brief summary
Researchers want to learn if using a study medicine called MK-1084 can help treat NSCLC. MK-1084 is a type of treatment called targeted therapy for the Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C gene change. The goal of this study is to learn about the safety of MK-1084 and to learn how many people have the cancer get smaller or go away during the study treatment.
Interventions
DRUGMK-1084
Oral Administration
BIOLOGICALPembrolizumab
Intravenous administration
BIOLOGICALCetuximab
Intravenous administration
DRUGCarboplatin
Intravenous administration
DRUGPemetrexed
Intravenous administration
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Some outcome measures will be assessed by blinded independent central review (BICR), with assessor(s) blinded to intervention assignment.
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 or cytologically confirmed diagnosis of advanced or metastatic nonsquamous Non-Small Cell Lung Cancer (NSCLC) * Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C mutations * Can provide an archival tumor tissue sample or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated * Has recovered to ≤Grade 1 or baseline from any Adverse events (AEs) due to previous anticancer therapies and/or ≤Grade 2 neuropathy and/or endocrine-related AEs adequately treated with hormone replacement * Has well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if HIV-infected * Has undetectable hepatitis B (HBV) viral load and have received HBV antiviral therapy for at least 4 weeks if hepatitis B surface antigen (HBsAg) positive * Has undetectable hepatitis C (HCV) viral load if HCV-infected
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants with a Dose Limiting Toxicity (DLT) | Up to approximately 21 days | A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration, excluding toxicities clearly not related to the drug. |
| Percentage of Participants who Experience at Least One Adverse Event (AE) | Up to approximately 84 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Percentage of Participants who Discontinue Study Intervention Due to an AE | Up to approximately 84 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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. |
| Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR) | Up to approximately 84 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) per RECIST 1.1 as assessed by BICR | Up to approximately 84 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented. |
| Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR | Up to approximately 84 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented. |
| Overall Survival (OS) | Up to approximately 84 months | OS, defined as the time from first dose or randomization (depending on study period) to death due to any cause. OS will be presented. |
| Area Under the Concentration-Time Curve (AUC) for MK-1084 | At designated timepoints (up to approximately 44 days) | Blood samples will be collected to determine the AUC of MK-1084. |
| Maximum Concentration (Cmax) of MK-1084 | At designated timepoints (up to approximately 44 days) | Blood samples will be collected to estimate Cmax of MK-1084. |
| Trough Concentration (Ctrough) of MK-1084 | At designated timepoints (up to approximately 84 months) | Blood samples will be collected to determine the Ctrough of MK-1084. |
Countries
Finland, Netherlands, South Korea, Turkey (Türkiye), Ukraine, United States
Contacts
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
CONTACTToll Free Number
Outcome results
None listed