A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)
KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations
Merck Sharp & Dohme LLC
190 participants
Mar 23, 2026
INTERVENTIONAL
Conditions
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
Eligibility
Inclusion Criteria6
- 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
- Provides archival tumor tissue sample of a tumor lesion not previously irradiated
- Has provided tissue prior to treatment allocation/randomization from a newly obtained 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 Criteria15
- 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 previous treatment with an agent targeting KRAS
- 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 history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
- Has an active infection requiring systemic therapy
- Have not adequately recovered from major surgery or have ongoing surgical complications
Interventions
Oral administration
IV infusion
IV Infusion
IV Infusion
Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are histamine -1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent) for prevention of chemotherapy induced nausea and vomiting.
Locations(3)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07286149