Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Programmed Cell Death-1 (PD1, PD-1), Programmed Death-Ligand 1 (PDL1, PD-L1)
Brief summary
The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) with or without chemotherapy in combination with vibostolimab (MK-7684), boserolimab (MK-5890), MK-4830, MK-0482, I-DXd, or HER3-DXd in treatment-naïve participants with advanced squamous or non-squamous NSCLC. This study is one of the pembrolizumab substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).
Detailed description
The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798
Interventions
BIOLOGICALPembrolizumab
IV infusion
DRUGCarboplatin
IV infusion
DRUGPaclitaxel
IV infusion
DRUGPemetrexed
IV infusion
BIOLOGICALVibostolimab
IV infusion
BIOLOGICALBoserolimab
IV infusion
BIOLOGICALMK-4830
IV infusion
BIOLOGICALMK-0482
IV Infusion
BIOLOGICALIfinatamab Deruxtecan (I-DXd)
IV infusion
BIOLOGICALHER3-DXd
IV Infusion
Sponsors
Merck Sharp & Dohme LLC
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Only participants in Part A will be randomized.
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 Stage IV squamous or nonsquamous NSCLC * Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy * Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation * Has not received prior systemic treatment for their metastatic NSCLC * Is able to complete all screening procedures within the 35-day screening window for Part A and 28-day screening window for Part B
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) | Up to approximately 24 months | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be reported. |
| Part B: Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 27 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported. |
| Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE) | Up to approximately 24 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be reported. |
| Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) | Up to approximately 3 Weeks | A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Progression-Free Survival (PFS) According to RECIST 1.1 | Up to approximately 24 months | PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per 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 will be reported. |
| Part A: Number of Participants Who Experience One or More AEs | Up to approximately 27 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported. |
| Part A: Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 24 months | An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be reported. |
| Part B: ORR per RECIST 1.1 as assessed by blinded independent central review (BICR) | Up to approximately 24 months | ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be reported. |
| Part B: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR | Up to approximately 24 months | For participants who show confirmed CR or PR, DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. DOR will be reported. |
| Part B: Cmax of I-DXd | At designated time points up to approximately 2 years | Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of I-DXd. |
| Part B: Cmax of HER3-DXd | At designated time points up to approximately 2 years | Cmax is the maximum concentration of the drug observed in plasma. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of HER3-DXd. |
| Part B: Cmax of pembrolizumab | At designated time points up to approximately 2 years | Cmax is the maximum concentration of the drug observed in serum. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Cmax of pembrolizumab. |
| Part B: Ctrough of I-DXd | At designated time points up to approximately 2 years | Ctrough is defined as the lowest observed concentration of drug in plasma at the end of the dosing interval. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough of I-DXd. |
| Part B: Ctrough of HER3-DXd | At designated time points up to approximately 2 years | Ctrough is defined as the lowest observed concentration of drug in plasma at the end of the dosing interval. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough of HER3-DXd. |
| Part B: Ctrough of pembrolizumab | At designated time points up to approximately 2 years | Ctrough is defined as the lowest observed concentration of drug in serum at the end of the dosing interval. Blood samples collected pre dose and at multiple timepoints post dose will be used to determine Ctrough of pembrolizumab. |
Countries
Hungary, Israel, Italy, Poland, South Korea, Spain, Taiwan, Ukraine, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed