Substudy 01I: A Study of Investigational Agents in Participants With Previously Treated Stage IV Squamous Non-small Cell Lung Cancer (NSCLC) (MK-3475-01I/KEYMAKER-U01I)

Study summary

Researchers are looking for other ways to treat metastatic squamous non-small cell lung cancer (NSCLC). Squamous NSCLC is cancer that starts in squamous cells, which are flat cells that line the inside of the airways in the lungs. Metastatic means the cancer has spread to other parts of the body. Standard treatment (usual treatment) for metastatic squamous NSCLC is immunotherapy with or without chemotherapy. Immunotherapy is a treatment that helps the immune system fight cancer. Chemotherapy is medicine that destroys cancer cells or stops them from growing. However, standard treatment may not work or may stop working to treat metastatic squamous NSCLC. Researchers want to learn if study treatments that are antibody drug conjugates (ADCs) can treat metastatic squamous NSCLC that did not respond (get smaller or go away) to standard treatment. An ADC attaches to a protein on cancer cells and delivers treatment to destroy those cells. The main goals of this study are to learn about: * The cancer response to the study treatments compared to chemotherapy * The safety of the study treatments and if people tolerate them This study is one of the substudies being conducted under one pembrolizumab umbrella master protocol (MK-3475-U01/KEYMAKER-U01).

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Key things to know

Main goalTreatment

This describes the study’s primary purpose.

What is being studiedR-DXD and I-DXD

Plus 3 other study approaches.

Who it may be forNon-small cell lung cancer (NSCLC) · Metastatic or stage IV

These are broad labels—not an eligibility decision.

Checked against the public recordLast updated Oct 7, 2026 · Source: ClinicalTrials.gov

Is enrollment open?Recruiting

The study is currently accepting participants.

What kind of study?Phase 2

Interventional

Where is it offered?46 U.S. locations

Locations may change over time.

Who runs it?Merck Sharp & Dohme LLC

Study sponsor

Study overview

What this study is about

Purpose: Treatment
Study type: Interventional
Phase: Phase 2
Sponsor: Merck Sharp & Dohme LLC
Interventions being studied: Biological: R-DXD; Biological: I-DXD; Drug: Docetaxel; Drug: Rescue Medications; Drug: Rescue Medication

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How this study is categorized

These labels come from structured fields and exact terms in the public record.

Cancer type

Non-small cell lung cancer (NSCLC)→

Disease setting

Metastatic or stage IV→

Treatment approach

Immunotherapy→Chemotherapy→

Study topics

After prior treatment→

Public criteria

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.

Requirements people may need to meetInclusion criteria

The main inclusion criteria include but are not limited to the following:
Histologically or cytologically confirmed diagnosis of Stage IV squamous non-small cell lung cancer (NSCLC)
Has documented disease progression per Response Evaluation Criteria In Solid Tumors 1.1 (RECIST 1.1), as assessed by investigator after receiving an anti-programmed cell death protein 1 (anti-PD-1)/programmed cell death ligand 1 (PD-L1) treatment and platinum-based chemotherapy for Stage IV disease
Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (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
Participants with history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable

Reasons someone may not be able to joinExclusion criteria

The main

Important: This is the sponsor’s public criteria, not a determination of eligibility. The study team must review your individual situation.

Study sites

U.S. locations

University of Kentucky Chandler Medical Center ( Site 0019)Lexington, Kentucky
MedStar Franklin Square Medical Center ( Site 0033)Baltimore, Maryland
Texas Oncology - DFW ( Site 8003)Dallas, Texas
Virginia Cancer Specialists (VCS) ( Site 0408)Fairfax, Virginia
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
Beijing Cancer Hospital ( Site 0301)Beijing, Beijing Municipality
Chongqing University Cancer Hospital ( Site 0304)Chongqing, Chongqing Municipality
Fujian Provincial Cancer Hospital ( Site 0310)Fuzhou, Fujian
Guangxi Medical University Cancer Hospital ( Site 0303)Nanning, Guangxi
Henan Cancer Hospital ( Site 0311)Zhengzhou, Henan

Source and freshness
Processed from ClinicalTrials.gov. Last public update: Oct 7, 2026. Always confirm current availability with the study team.

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