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NCT07286149PHASE1, PHASE2Recruiting

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)

Merck Sharp & Dohme LLC

Start Date

4/30/2026

Completion Date

4/13/2032

Summary

Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn: * About the safety of MK-1084 and if people tolerate it when taken with other treatments * How many people have the cancer respond (get smaller or go away) to the treatments

Detailed Description

This is a substudy of the master protocol MK-3475-U01 (KEYMAKER-U01) - NCT04165798. Per amendment 3, the MK-1084 + Cetuximab arm was discontinued.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: The main inclusion criteria include but are not limited to the following: * Has histologically or cytologically confirmed diagnosis of advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) * Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene (KRAS) mutation of glycine to cysteine at codon 12 (G12C) mutations * Has documented disease progression after receiving 1-2 prior lines of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy and platinum-based chemotherapy * Has provided tumor tissue for biomarker analysis from an archival sample or a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated * Participants with human immunodeficiency virus (HIV) infection must have well-controlled HIV on antiretroviral therapy (ART) per protocol Exclusion Criteria: The main exclusion criteria include but are not limited to the following: * Has a diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements * Has clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis * Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease * Has evidence of any leptomeningeal disease * Has uncontrolled or significant cardiovascular disorder or cerebrovascular disease prior to allocation/randomization * Has one or more of the following ophthalmological conditions: a) Clinically significant corneal disease b) history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis * HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention * Has known additional malignancy that is progressing or has required active treatment within the past 3 years * Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use or current ILD, or suspected ILD * Has an active infection requiring systemic therapy * Has not adequately recovered from major surgery or has ongoing surgical complications

Interventions

DRUG

MK-1084

BIOLOGICAL

Patritumab deruxtecan

BIOLOGICAL

Sacituzumab tirumotecan

BIOLOGICAL

Cetuximab

DRUG

Rescue Medications

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Conditions

Lung Neoplasm Malignant

Locations

Clermont Oncology Center ( Site 0041)

Clermont, Florida 34711

United States

University of Illinois Hospital & Health Sciences System ( Site 0044)

Chicago, Illinois 60612

United States

Providence Portland Medical Center ( Site 0043)

Portland, Oregon 97213

United States

Providence Oncology and Hematology Care Clinic - Westside ( Site 0059)

Portland, Oregon 97225

United States

Hospital São Lucas da PUCRS ( Site 0283)

Porto Alegre, Rio Grande do Sul 90610-000

Brazil

Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0282)

Barretos, São Paulo 14784-400

Brazil

Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0286)

São José do Rio Preto, São Paulo 15090-000

Brazil

Hospital Paulistano ( Site 0280)

São Paulo, São Paulo 01321001

Brazil

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0162)

Santiago, Region M. de Santiago 7500653

Chile

FALP ( Site 0161)

Santiago, Region M. de Santiago 7500921

Chile

Bradfordhill ( Site 0160)

Santiago, Region M. de Santiago 8420383

Chile

Guangdong Provincial People s Hospital ( Site 0300)

Guangzhou, Guangdong 510120

China

UniversitaetsklInikum Tuebingen ( Site 0192)

Tübingen, Baden-Wurttemberg 72076

Germany

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

Athens, Attica 115 27

Greece

Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 0205)

Athens, Attica 115 28

Greece

Queen Mary Hospital ( Site 0230)

Hong Kong, 000000

Hong Kong

Hong Kong United Oncology Centre ( Site 0232)

Jordan, 000000

Hong Kong

Prince of Wales Hospital ( Site 0231)

Shatin,

Hong Kong

Shaare Zedek Medical Center ( Site 0186)

Jerusalem, 9103102

Israel

Sheba Medical Center ( Site 0180)

Ramat Gan, 5265601

Israel

IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0176)

Meldola, Forli-Cesena 47014

Italy

Severance Hospital, Yonsei University Health System ( Site 0080)

Seoul, 03722

South Korea

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

Hospitalet, Barcelona 08908

Spain

Hospital Clinic de Barcelona ( Site 0092)

Barcelona, 08036

Spain

Hospital Universitario Virgen Macarena ( Site 0093)

Seville, 41009

Spain