ACTIVE_NOT_RECRUITING

Study of Pembrolizumab (MK-3475) Monotherapy Versus Sacituzumab Govitecan in Combination With Pembrolizumab for Participants With Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-3475-D46)

Conditions

Carcinoma, Non-Small-Cell Lung Programmed Cell Death-1 (PD1, PD-1)Programmed Death-Ligand 1 (PDL1, PD-L1)Programmed Cell Death-2 (PD2, PD-2)Programmed Death-Ligand 2 (PDL2, PD-L2)Trophoblast Cell Surface Antigen-2 (TROP-2)Antibody-Drug Conjugate (ADC)

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to compare pembrolizumab (MK-3475) in combination with sacituzumab govitecan with pembrolizumab alone with respect to progression-free survival (PFS) and overall survival (OS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as assessed by blinded independent central review (BICR) among adults with metastatic non-small cell lung cancer (NSCLC) with programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%).

Official Title

An Open-label, Multicenter, Phase 3 Randomized, Active-Comparator-Controlled Clinical Study of Pembrolizumab (MK-3475) in Combination With Sacituzumab Govitecan Versus MK-3475 Monotherapy as First-line Treatment in Participants With PD L1 TPS Greater Than or Equal to 50% Metastatic Non-small Cell Lung Cancer (KEYNOTE D46/EVOKE-03)

Quick Facts

Study Start:2023-02-06

Study Completion:2028-08-23

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT05609968

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC) * Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy * Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) ≥50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory * Has a life expectancy of at least 3 months	* Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years * Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC * Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy * Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor * Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids * Has received radiation therapy to the lung that is \>30 Gray (Gy) within 6 months of the first dose of study intervention * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration * Has cardiac disease * Myocardial infarction or unstable angina pectoris within 6 months of enrollment * History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation * New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \<40% * Has active chronic inflammatory bowel disease * Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients * Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy * History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease * Has active infection requiring systemic therapy * Has history of human immunodeficiency virus (HIV) infection * History of hepatitis B or known active hepatitis C virus infection * Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator * Have not adequately recovered from major surgery or have ongoing surgical complications

Inclusion Criteria

Exclusion Criteria

* Has a histologically or cytologically confirmed diagnosis of metastatic non-small cell lung cancer (NSCLC)
* Has confirmation that epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase 1 (ALK-1), or ROS proto-oncogene 1 (ROS-1)-directed therapy is not indicated as primary therapy
* Has provided tumor tissue that demonstrates PD-L1 tumor proportion score (TPS) ≥50% of tumor cells as assessed by immunohistochemistry (IHC) at a central laboratory
* Has a life expectancy of at least 3 months

* Has history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
* Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
* Has previously received treatment with Topoisomerase 1 inhibitors or Trop-2 targeted therapy
* Has received prior therapy with an anti-programmed cell death 1 protein (anti-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti anti- programmed cell death ligand 2 (PD-L2) agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor
* Has received prior radiotherapy within 2 weeks of start of study intervention or has radiation-related toxicities requiring corticosteroids
* Has received radiation therapy to the lung that is \>30 Gray (Gy) within 6 months of the first dose of study intervention
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received an investigational agent or has used an investigational device within 4 weeks before study intervention administration
* Has cardiac disease
* Myocardial infarction or unstable angina pectoris within 6 months of enrollment
* History of serious ventricular arrhythmia, high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications; history of QT interval prolongation
* New York Heart Association (NYHA) Class III or greater congestive heart failure or left ventricular ejection fraction of \<40%
* Has active chronic inflammatory bowel disease
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
* Has severe hypersensitivity (≥Grade 3) to pembrolizumab or sacituzumab govitecan and/or any of their excipients
* Has active autoimmune disease that has required systemic treatment in past 2 years except replacement therapy
* History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Has active infection requiring systemic therapy
* Has history of human immunodeficiency virus (HIV) infection
* History of hepatitis B or known active hepatitis C virus infection
* Has history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator
* Have not adequately recovered from major surgery or have ongoing surgical complications

Contacts and Locations

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

Infirmary Cancer Care ( Site 0418)

Mobile, Alabama, 36607

United States

Profound Research LLC ( Site 0444)

Oceanside, California, 92056-4522

United States

Clermont Oncology Center ( Site 0421)

Clermont, Florida, 34711

United States

University of Miami Hospital and Clinics, Sylvester Cancer Center ( Site 0417)

Miami, Florida, 33136

United States

Mid Florida Hematology and Oncology Center ( Site 0416)

Orange City, Florida, 32763

United States

Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital-Research ( Site 0407)

Marietta, Georgia, 30060

United States

Our Lady of the Lake RMC ( Site 0424)

Baton Rouge, Louisiana, 70808

United States

Henry Ford Hospital ( Site 0412)

Detroit, Michigan, 48202

United States

Profound Research LLC ( Site 0440)

Farmington Hills, Michigan, 48334

United States

Allina Health Cancer Institute - Abbott Northwestern Hospital ( Site 0425)

Minneapolis, Minnesota, 55407

United States

Basil Clinical ( Site 0441)

Inwood, New York, 11096

United States

White Plains Hospital-Center for Cancer Care ( Site 0403)

White Plains, New York, 10601

United States

Kaiser Permanente Northwest-Central Interstate--Oncology ( Site 0408)

Portland, Oregon, 97227

United States

Oregon Health & Science University ( Site 0427)

Portland, Oregon, 97239

United States

Houston Methodist Hospital ( Site 0419)

Houston, Texas, 77030

United States

Central Texas Veterans health care ( Site 0414)

Temple, Texas, 76504

United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-02-06

Study Completion Date2028-08-23

Study Record Updates

Study Start Date2023-02-06

Study Completion Date2028-08-23

Terms related to this study

Keywords Provided by Researchers

Programmed Cell Death-1 (PD1, PD-1)
Programmed Death-Ligand 1 (PDL1, PD-L1)
Programmed Cell Death-2 (PD2, PD-2)
Programmed Death-Ligand 2 (PDL2, PD-L2)
Trophoblast Cell Surface Antigen-2 (TROP-2)
Antibody-Drug Conjugate (ADC)

Additional Relevant MeSH Terms

Carcinoma, Non-Small-Cell Lung