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

Recruiting now · Phase 2

Conditions studied: Carcinoma, Non-Small-Cell Lung

In brief

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

Key facts

Study ID: NCT06780085
Run by: Merck Sharp & Dohme LLC
People needed: 96
Starts: 2025-05-13
Expected to finish: 2032-03-12
Last updated by the study team: 2026-07-06

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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

You may not qualify if…

The main exclusion criteria include but are not limited to the following:
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 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 previously received docetaxel as monotherapy or in combination with other therapies
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 untreated central nervous system (CNS) metastases and/or carcinomatous meningitis
Has evidence of any leptomeningeal disease
Has history of interstitial lung disease (ILD)/pneumonitis, current diagnosis of ILD, and/or suspected ILD
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 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

Where it is running

University of Kentucky Chandler Medical Center ( Site 0019) — Lexington, Kentucky, United States (enrolling)
MedStar Franklin Square Medical Center ( Site 0033) — Baltimore, Maryland, United States (enrolling)
AHN Cancer Institute - Allegheny General ( Site 9501) — Pittsburgh, Pennsylvania, United States (enrolling)
Centro de Estudios Clínicos SAGA ( Site 0161) — Santiago, Region M. de Santiago, Chile (enrolling)
FALP ( Site 0160) — Santiago, Region M. de Santiago, Chile (enrolling)
Bradfordhill ( Site 0162) — Santiago, Region M. de Santiago, Chile (enrolling)
Universitaetsklinik Tuebingen ( Site 0192) — Tübingen, Baden-Wurttemberg, Germany (enrolling)
Charite-Universitaetsmedizin Berlin ( Site 0191) — Berlin, Germany (enrolling)
THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA"-3rd Dept of Internal Medicine and Laboratory, Oncol ( Site 0204) — Athens, Attica, Greece (enrolling)
European Interbalkan Medical Center ( Site 0205) — Thessaloniki, Greece (enrolling)
Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063) — Kecskemét, Bács-Kiskun county, Hungary (enrolling)
Petz Aladar Egyetemi Oktato Korhaz ( Site 0062) — Győr, Győr-Moson-Sopron, Hungary (enrolling)
Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061) — Szolnok, Jász-Nagykun-Szolnok, Hungary (enrolling)
Rambam Health Care Campus ( Site 0076) — Haifa, Israel (enrolling)
Shaare Zedek Medical Center ( Site 0075) — Jerusalem, Israel (enrolling)
Meir Medical Center ( Site 0071) — Kfar Saba, Israel (enrolling)
Rabin Medical Center ( Site 0074) — Petah Tikva, Israel (enrolling)
Sheba Medical Center ( Site 0070) — Ramat Gan, Israel (enrolling)
Sourasky Medical Center ( Site 0077) — Tel Aviv, Israel (enrolling)
Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175) — Milan, Lombardy, Italy (enrolling)
Azienda Ospedaliera Universitaria Careggi ( Site 0173) — Florence, Italy (enrolling)
Ospedale San Raffaele. ( Site 0171) — Milan, Italy (enrolling)
Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174) — Roma, Italy (enrolling)
Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0153) — Poznan, Greater Poland Voivodeship, Poland (enrolling)
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0151) — Warsaw, Masovian Voivodeship, Poland (enrolling)

Full record on ClinicalTrials.gov

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