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NCT06780098PHASE2Recruiting

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)

Merck Sharp & Dohme LLC

Start Date

5/28/2025

Completion Date

3/2/2032

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).

Detailed Description

The master screening protocol is MK-3475-U01 (KEYMAKER-U01) - NCT04165798

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion 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 Exclusion Criteria: 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 * Has uncontrolled or significant cardiovascular disorder * Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc), or any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren's syndrome, sarcoidosis, etc), or prior pneumonectomy * Participants who have adverse events (AEs) (other than alopecia) due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline * Has clinically significant corneal disease * Has previously received docetaxel as monotherapy or in combination with other therapies * 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 * Evidence of any leptomeningeal disease * Has one or more of the following indicators of interstitial lung disease (ILD)/pneumonitis: any history of ILD/pneumonitis irrespective of steroid use (except for a history of radiation pneumonitis that did not require steroids), current diagnosis of ILD, clinical or radiographic suspicion of ILD * Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed * Active infection requiring systemic therapy * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) * Known history of, or active, neurologic paraneoplastic syndrome * History of allogeneic tissue/solid organ transplant * Has not adequately recovered from major surgery or have ongoing surgical complications

Interventions

BIOLOGICAL

R-DXD

BIOLOGICAL

I-DXD

DRUG

Docetaxel

DRUG

Rescue Medications

DRUG

Rescue Medication

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Conditions

Lung Neoplasm

Locations

University of Kentucky Chandler Medical Center ( Site 0019)

Lexington, Kentucky 40536-0293

United States

MedStar Franklin Square Medical Center ( Site 0033)

Baltimore, Maryland 21237

United States

Texas Oncology - DFW ( Site 8003)

Dallas, Texas 75246-2046

United States

Centro de Estudios Clínicos SAGA ( Site 0161)

Santiago, Region M. de Santiago 7500653

Chile

FALP ( Site 0160)

Santiago, Region M. de Santiago 7500921

Chile

Bradfordhill ( Site 0162)

Santiago, Region M. de Santiago 8420383

Chile

Beijing Cancer Hospital ( Site 0301)

Beijing, Beijing Municipality 100142

China

Chongqing University Cancer Hospital ( Site 0304)

Chongqing, Chongqing Municipality 400030

China

Fujian Provincial Cancer Hospital ( Site 0310)

Fuzhou, Fujian 350014

China

Guangxi Medical University Cancer Hospital ( Site 0303)

Nanning, Guangxi 530201

China

Henan Cancer Hospital ( Site 0311)

Zhengzhou, Henan 450000

China

Nanjing Drum Tower Hospital JiangBei International Branch Hospital ( Site 0309)

Nanjing, Jiangsu 210031

China

Shanghai Chest Hospital ( Site 0308)

Shanghai, Shanghai Municipality 200030

China

Shanghai Pulmonary Hospital ( Site 0300)

Shanghai, Shanghai Municipality 200433

China

UniversitaetsklInikum Tuebingen ( Site 0192)

Tübingen, Baden-Wurttemberg 72076

Germany

Charite-Universitaetsmedizin Berlin ( Site 0191)

Berlin, 13353

Germany

EVANGELISMOS S.A ( Site 0206)

Athens, Attica 106 76

Greece

THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA" ( Site 0204)

Athens, Attica 115 27

Greece

European Interbalkan Medical Center-Oncology Department ( Site 0205)

Thessaloniki, 570 01

Greece

Bacs-Kiskun Varmegyei Oktatokorhaz ( Site 0063)

Kecskemét, Bács-Kiskun county 6000

Hungary

Petz Aladar Egyetemi Oktato Korhaz ( Site 0062)

Győr, Győr-Moson-Sopron 9024

Hungary

Jasz-Nagykun-Szolnok Varmegyei Hetenyi Geza Korhaz-Rendelointezet ( Site 0061)

Szolnok, Jász-Nagykun-Szolnok 5000

Hungary

Rambam Health Care Campus ( Site 0076)

Haifa, 3109601

Israel

Shaare Zedek Medical Center ( Site 0075)

Jerusalem, 9103102

Israel

Meir Medical Center ( Site 0071)

Kfar Saba, 4428164

Israel

Rabin Medical Center ( Site 0074)

Petah Tikva, 4941492

Israel

Sheba Medical Center ( Site 0070)

Ramat Gan, 5265601

Israel

Sourasky Medical Center ( Site 0077)

Tel Aviv, 6423906

Israel

Azienda Ospedaliera Universitaria Careggi ( Site 0173)

Florence, 50134

Italy

Ospedale San Raffaele. ( Site 0171)

Milan, 20132

Italy

Fondazione IRCCS Istituto Nazionale dei Tumori ( Site 0175)

Milan, 20133

Italy

Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore ( Site 0174)

Roma, 00168

Italy

Wielkopolskie Centrum Pulmonologii i Torakochirurgii ( Site 0153)

Poznan, Greater Poland Voivodeship 60-569

Poland

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie ( Site 0151)

Warsaw, Masovian Voivodeship 02-781

Poland

Uniwersyteckie Centrum Kliniczne-Early Clinical Trials Unit ( Site 0150)

Gdansk, Pomeranian Voivodeship 80-214

Poland

Szpital Wojewódzki im. Mikoaja Kopernika w Koszalinie ( Site 0152)

Koszalin, West Pomeranian Voivodeship 75-581

Poland

Institut Català d'Oncologia - L'Hospitalet ( Site 0090)

L'Hospitalet de Llobregat, Barcelona 08908

Spain

Hospital Clinic de Barcelona ( Site 0092)

Barcelona, 08008

Spain

Hospital Universitario Quiron Madrid ( Site 0091)

Madrid, 28223

Spain

Ege Universitesi Hastanesi ( Site 0143)

Izmir, İzmir 35100

Turkey (Türkiye)

Baskent University Dr. Turgut Noyan Research and Training Center-ONCOLOGY ( Site 0141)

Adana, 01250

Turkey (Türkiye)

Hacettepe Universitesi Tip Fakultesi Hastanesi ( Site 0140)

Ankara, 06230

Turkey (Türkiye)

Ankara Bilkent Şehir Hastanesi. ( Site 0142)

Ankara, 06800

Turkey (Türkiye)

Istanbul Universitesi Cerrahpasa Tip Fakultesi ( Site 0144)

Istanbul, 34098

Turkey (Türkiye)