KEYMAKER-U01 Substudy 01A: A Phase 1/2, Umbrella Study With Rolling Arms of Investigational Agents With Pembrolizumab With or Without Chemotherapy in Treatment-Naive Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)
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
Arms & 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
Outcome measures
Primary
Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
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.
Time frame: Up to approximately 24 months
Part B: Number of Participants Who Experience One or More Adverse Events (AEs)
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.
Time frame: Up to approximately 27 months
Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE)
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.
Time frame: Up to approximately 24 months
Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
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.
Time frame: Up to approximately 3 Weeks
Secondary
Part A: Progression-Free Survival (PFS) According to RECIST 1.1
Time frame: Up to approximately 24 months
Part A: Number of Participants Who Experience One or More AEs
Time frame: Up to approximately 27 months
Part A: Number of Participants Who Discontinue Study Treatment Due to an AE
Time frame: Up to approximately 24 months
Part B: ORR per RECIST 1.1 as assessed by blinded independent central review (BICR)
Time frame: Up to approximately 24 months
Part B: Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
Time frame: Up to approximately 24 months
Part B: Cmax of I-DXd
Time frame: At designated time points up to approximately 2 years
Part B: Cmax of HER3-DXd
Time frame: At designated time points up to approximately 2 years
Part B: Cmax of pembrolizumab
Time frame: At designated time points up to approximately 2 years
Part B: Ctrough of I-DXd
Time frame: At designated time points up to approximately 2 years
Part B: Ctrough of HER3-DXd
Time frame: At designated time points up to approximately 2 years
Part B: Ctrough of pembrolizumab
Time frame: At designated time points up to approximately 2 years
Eligibility criteria
Study locations (18)
Banner MD Anderson Cancer Center ( Site 0001)
Gilbert, Arizona, 85234
City of Hope ( Site 0014)
Duarte, California, 91010
UCSF Medical Center at Mission Bay ( Site 0007)
San Francisco, California, 94158
Georgetown University ( Site 0036)
Washington D.C., District of Columbia, 20007
University of Kentucky Markey Cancer Center ( Site 0019)
Lexington, Kentucky, 40536-0293
MedStar Franklin Square Medical Center ( Site 0033)
Baltimore, Maryland, 21237
Massachusetts General Hospital ( Site 0003)
Boston, Massachusetts, 02114
Dana Farber Cancer Institute ( Site 0002)
Boston, Massachusetts, 02215
Oncology Hematology West, PC DBA Nebraska Cancer Specialists ( Site 0031)
Omaha, Nebraska, 68130
Dartmouth Hitchcock Medical Center ( Site 0016)
Lebanon, New Hampshire, 03766
John Theurer Cancer Center at Hackensack University Medical Center ( Site 0037)
Hackensack, New Jersey, 07601
Laura and Isaac Perlmutter Cancer Center ( Site 0034)
New York, New York, 10016
Sanford Fargo Medical Center ( Site 0039)
Fargo, North Dakota, 58102
Cleveland Clinic Main ( Site 0006)
Cleveland, Ohio, 44195
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C ( Site 0015)
Columbus, Ohio, 43210
Abramson Cancer Center of the University of Pennsylvania ( Site 0010)
Philadelphia, Pennsylvania, 19104
Sanford Cancer Center ( Site 0038)
Sioux Falls, South Dakota, 57104
The University of Texas MD Anderson Cancer Center ( Site 0009)
Houston, Texas, 77030