RECRUITING

A Study of Pembrolizumab With or Without Chemotherapy in Combination With Additional Treatments for Advanced Non-Small Cell Lung Cancer (NSCLC) (MK-3475-01G/KEYMAKER U01)

Conditions

Non-small Cell Lung Cancer Lung Neoplasms Lung Cancer Pulmonary Neoplasms Pulmonary Cancer Non-Small Cell Lung Carcinoma

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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

Researchers are investigating new treatments for untreated advanced non-small cell lung cancer (NSCLC), which is the most common form of lung cancer and lung cancer that has spread beyond surgical removal. Standard treatments include immunotherapy, such as pembrolizumab, and chemotherapy. This study aims to determine the effectiveness of adding other treatments, including the human epidermal growth factor receptor 3-directed antibody-drug conjugate (HER3-DXd) patritumab deruxtecan, to pembrolizumab, with or without chemotherapy. The primary goals are to assess safety and efficacy of the treatments.

Official Title

KEYMAKER-U01 Substudy 01G: A Phase 2, Umbrella Study With Rolling Arms of Investigational Agents in Combination With Pembrolizumab With or Without Platinum-based Chemotherapy in Treatment-Naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC)

Quick Facts

Study Start:2025-03-10

Study Completion:2032-03-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06731907

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
* Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8. * Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization. * Has archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided. * Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on ART. * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment randomization.	* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements. * Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement. * Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement. * Has evidence of any leptomeningeal disease. * Has known history of, or active, neurologic paraneoplastic syndrome. * Has clinically significant corneal disease. * Has myocardial infarction within 6 months. * Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure. * Has uncontrolled angina pectoris within 6 months. * Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment. * Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes. * Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker. * Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers. * Has coronary/peripheral artery bypass graft within 6 months. * Has complete left bundle branch block. * Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization. * Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor. * Has received prior systemic anticancer therapy for their metastatic NSCLC. * Has received prior therapy with an anti- programmed cell death 1 protein (anti-PD-1), anti- programmed cell death ligand 1 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-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 toxicity requiring corticosteroids. * Has received radiation therapy to the lung that is \>30 gray within 6 months of start of study intervention. * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. * Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention. * Has known additional malignancy that is progressing or has required active treatment within the past 3 years. * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. * Has severe hypersensitivity to any of the study interventions and/or any of their excipients. * Has active autoimmune disease that has required systemic treatment in the past 2 years. * Has active infection requiring systemic therapy. * Has concurrent active Hepatitis B and Hepatitis C virus infection. * Have not adequately recovered from major surgery or have ongoing surgical complications.

Inclusion Criteria

Exclusion Criteria

* Histologically or cytologically confirmed diagnosis of Stage IV squamous or non-squamous non-small cell lung cancer (NSCLC) per American Joint Committee on Cancer (AJCC) Staging Manual Version 8.
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1 as assessed within 7 days before randomization.
* Has archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
* Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on ART.
* Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to treatment randomization.

* Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements.
* Participants with squamous histology are excluded if there is a known tumor-activating epidermal growth factor receptor (EGFR) mutation or anaplastic lymphoma kinase (ALK) or c ros oncogene 1 (ROS1) gene rearrangement.
* Is HIV-infected with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder, or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement.
* Has evidence of any leptomeningeal disease.
* Has known history of, or active, neurologic paraneoplastic syndrome.
* Has clinically significant corneal disease.
* Has myocardial infarction within 6 months.
* Has New York Heart Association (NYHA) Classes 3 or 4 congestive heart failure.
* Has uncontrolled angina pectoris within 6 months.
* Has cardiac arrhythmia requiring ongoing antiarrhythmic treatment.
* Has history of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes.
* Has bradycardia of less than 50 beats per minute (bpm) unless the participant has a pacemaker.
* Has history of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
* Has coronary/peripheral artery bypass graft within 6 months.
* Has complete left bundle branch block.
* Has inadequate washout period from prior concomitant therapy as specified in protocol before randomization.
* Has received prior treatment with a topoisomerase I inhibitor or an anti-HER3 antibody and/or ADC that consists of an exatecan derivative that is a topoisomerase I inhibitor.
* Has received prior systemic anticancer therapy for their metastatic NSCLC.
* Has received prior therapy with an anti- programmed cell death 1 protein (anti-PD-1), anti- programmed cell death ligand 1 protein (anti-PD-L1), or anti- programmed cell death ligand 2 protein (anti-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 toxicity requiring corticosteroids.
* Has received radiation therapy to the lung that is \>30 gray within 6 months of start of study intervention.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Has diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
* Has known additional malignancy that is progressing or has required active treatment within the past 3 years.
* Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
* Has severe hypersensitivity to any of the study interventions and/or any of their excipients.
* Has active autoimmune disease that has required systemic treatment in the past 2 years.
* Has active infection requiring systemic therapy.
* Has concurrent active Hepatitis B and Hepatitis C virus infection.
* Have not adequately recovered from major surgery or have ongoing surgical complications.

Contacts and Locations

Study Contact

Toll Free Number

CONTACT

1-888-577-8839

Trialsites@msd.com

Principal Investigator

Medical Director

STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Study Locations (Sites)

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland, 21237

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 Date2025-03-10

Study Completion Date2032-03-12

Study Record Updates

Study Start Date2025-03-10

Study Completion Date2032-03-12

Terms related to this study

Keywords Provided by Researchers

Lung Neoplasms
Lung Cancer
Pulmonary Neoplasms
Pulmonary Cancer
Non-Small Cell Lung Carcinoma

Additional Relevant MeSH Terms

Non-small Cell Lung Cancer