RECRUITING

A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)

Conditions

Carcinoma, Non-Small-Cell Lung Programmed Cell Death-1 (PD1, PD-1)Programmed Death-Ligand 1 (PDL1, PD-L1)Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Quick Navigation

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 looking for new ways to treat metastatic nonsquamous non-small cell lung cancer (NSCLC) that has been treated before. Metastatic means the cancer has spread to other parts of the body. Nonsquamous means the cancer did not start in squamous cells, which are flat cells that line the inside of the lungs. Standard treatment (usual treatment) for NSCLC is surgery, then immunotherapy with or without chemotherapy after surgery. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is a medicine that works to destroy cancer cells or stop them from growing. However, standard treatment may not work or may stop working for some people. Researchers want to know if 2 antibody drug conjugates (ADCs) can help treat metastatic nonsquamous NSCLC that did not respond (get smaller or go away) to treatment. An ADC attaches to specific targets on cancers cells and delivers treatment to destroy those cells. Researchers will compare 2 different ADCs (the study treatments) to chemotherapy in this study. The goals of this study are to learn: * About the safety of the study treatments and if people tolerate them * How many people have the cancer respond to the study treatments

Official Title

KEYMAKER-U01 Substudy 01H: A Phase 2, Randomized, Umbrella Study With Rolling Arms of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC)

Quick Facts

Study Start:2025-05-13

Study Completion:2032-03-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06780085

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 nonsquamous non-small cell lung cancer (NSCLC) * Documented disease progression as assessed by investigator using RECIST 1.1 after receiving both anti-PD-(L)1 therapy and platinum-based chemotherapy per local standard of care. These can be given together or in sequence. * Confirmation per local test report that epidermal growth factor receptor negative (EGFR-), anaplastic lymphoma kinase negative (ALK-), or c ros oncogene 1 negative (ROS1-) directed therapy is not indicated as primary therapy * Measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR * Life expectancy of at least 3 months * An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization * Is an individual of any sex/gender who is at least 18 years of age at the time of providing the informed consent * Has adequate organ function * If capable of producing sperm refrains from donating sperm plus either abstains from penile-vaginal intercourse or uses a penile/external condom, with contraceptive use consistent with local regulations * Participant/participants of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test; and is not breastfeeding and uses a highly effective contraceptive method * Archival tumor tissue sample of a tumor lesion not previously irradiated has been provided * Has provided tissue prior to treatment randomization from a newly obtained formalin-fixed sample from a new biopsy * Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART) * Participants who are hepatitis B surface antigen (HBsAg) positive have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization * Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening	* Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements * Received radiation therapy to the lung * Has uncontrolled or significant cardiovascular disorder prior to randomization * Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses * Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline * Has known severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients * Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection (including HIV infection) * Has clinically significant corneal disease * Has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids * Has inadequate washout period prior to randomization * 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 * Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration * 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 evidence of any leptomeningeal disease * Has history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD, and/or suspected ILD/pneumonitis * Has active autoimmune disease that has required systemic treatment in the past 2 years * Has active infection requiring systemic therapy * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has concurrent active Hepatitis B and Hepatitis C virus infection * Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease * Has known history of, or active, neurologic paraneoplastic syndrome * Has history of allogeneic tissue/solid organ transplant * Have not adequately recovered from major surgery or have ongoing surgical complications * Participants who are incapacitated

Inclusion Criteria

Exclusion Criteria

* Histologically or cytologically confirmed diagnosis of Stage IV nonsquamous non-small cell lung cancer (NSCLC)
* Documented disease progression as assessed by investigator using RECIST 1.1 after receiving both anti-PD-(L)1 therapy and platinum-based chemotherapy per local standard of care. These can be given together or in sequence.
* Confirmation per local test report that epidermal growth factor receptor negative (EGFR-), anaplastic lymphoma kinase negative (ALK-), or c ros oncogene 1 negative (ROS1-) directed therapy is not indicated as primary therapy
* Measurable disease per RECIST 1.1 as assessed by investigator and verified by BICR
* Life expectancy of at least 3 months
* An Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
* Is an individual of any sex/gender who is at least 18 years of age at the time of providing the informed consent
* Has adequate organ function
* If capable of producing sperm refrains from donating sperm plus either abstains from penile-vaginal intercourse or uses a penile/external condom, with contraceptive use consistent with local regulations
* Participant/participants of childbearing potential (POCBP) is not pregnant and has a negative highly sensitive pregnancy test; and is not breastfeeding and uses a highly effective contraceptive method
* Archival tumor tissue sample of a tumor lesion not previously irradiated has been provided
* Has provided tissue prior to treatment randomization from a newly obtained formalin-fixed sample from a new biopsy
* Human Immunodeficiency Virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART)
* Participants who are hepatitis B surface antigen (HBsAg) positive have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization
* Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening

* Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements
* Received radiation therapy to the lung
* Has uncontrolled or significant cardiovascular disorder prior to randomization
* Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
* Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline
* Has known severe hypersensitivity (≥Grade 3) to study intervention and/or any of its excipients
* Has evidence of ongoing uncontrolled systemic bacterial, fungal, or viral infection (including HIV infection)
* Has clinically significant corneal disease
* Has received prior radiotherapy within 2 weeks of start of study intervention, or radiation related toxicities, requiring corticosteroids
* Has inadequate washout period prior to randomization
* 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
* Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
* 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 evidence of any leptomeningeal disease
* Has history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD, and/or suspected ILD/pneumonitis
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* Has active infection requiring systemic therapy
* HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has concurrent active Hepatitis B and Hepatitis C virus infection
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
* Has known history of, or active, neurologic paraneoplastic syndrome
* Has history of allogeneic tissue/solid organ transplant
* Have not adequately recovered from major surgery or have ongoing surgical complications
* Participants who are incapacitated

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 Date2025-05-13

Study Completion Date2032-03-12

Study Record Updates

Study Start Date2025-05-13

Study Completion Date2032-03-12

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 1 Ligand 2 (PDL2, PD-L2)

Additional Relevant MeSH Terms

Carcinoma, Non-Small-Cell Lung