A Study of Investigational Agents in Participants With Previously Treated Stage IV Nonsquamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01H/KEYMAKER-U01)
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
Ask AI to explain this studyKey things to know
This describes the study’s primary purpose.
Plus 4 other study approaches.
These are broad labels—not an eligibility decision.
Checked against the public recordLast updated Oct 27, 2026 · Source: ClinicalTrials.gov
The study is currently accepting participants.
Interventional
Locations may change over time.
Study sponsor
What this study is about
- Purpose
- Treatment
- Study type
- Interventional
- Phase
- Phase 2
- Sponsor
- Merck Sharp & Dohme LLC
- Interventions being studied
- Biological: Raludotatug Deruxtecan; Biological: Ifinatamab Deruxtecan; Drug: Docetetaxel; Drug: 5-hydroxytryptamine subtype 3 receptor antagonist; Drug: Neurokinin-1 receptor antagonist; Drug: Corticosteroid
How this study is categorized
These labels come from structured fields and exact terms in the public record.
Who may be able to participate
The sponsor separates these requirements into two groups. You do not need to interpret them alone—use them to guide a conversation with the study team.
- The main inclusion criteria include but are not limited to the following:
- Histologically or cytologically confirmed diagnosis of Stage IV nonsquamous non-small cell lung cancer (NSCLC)
- Documented disease progression per RECIST 1.1 after receiving an anti-programmed cell death 1 protein (PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy
- Confirmation per local test report that epidermal growth factor receptor negative (EGFR-), anaplastic lymphoma kinase negative (ALK-), c ros oncogene 1 negative (ROS1-), or other 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
The main
Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.
U.S. locations
- University of Kentucky Chandler Medical Center ( Site 0019)Lexington, Kentucky
- MedStar Franklin Square Medical Center ( Site 0033)Baltimore, Maryland
- AHN Cancer Institute - Allegheny General ( Site 9501)Pittsburgh, Pennsylvania
- Texas Oncology - DFW ( Site 8003)Dallas, Texas
- Centro de Estudios Clínicos SAGA ( Site 0161)Santiago, Region M. de Santiago
- Fundación Arturo López Pérez ( Site 0160)Santiago, Region M. de Santiago
- Bradfordhill ( Site 0162)Santiago, Region M. de Santiago
- Universitaetsklinik Tuebingen ( Site 0192)Tübingen, Baden-Wurttemberg
- Charite-Universitaetsmedizin Berlin ( Site 0191)Berlin
- THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204)Athens, Attica
- European Interbalkan Medical Center ( Site 0205)Thessaloniki
- Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063)Kecskemét, Bács-Kiskun county
Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 27, 2026. Always confirm current availability with the study team.