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RecruitingInterventionalPhase 1/Phase 2

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

NCT ID: NCT07286149Sponsor: Merck Sharp & Dohme LLCLast updated: 2026-06-18

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.

Arms & interventions

  • DrugMK-1084

    Oral administration

  • BiologicalPatritumab deruxtecan

    IV infusion

  • BiologicalSacituzumab tirumotecan

    IV Infusion

  • BiologicalCetuximab

    IV Infusion

  • DrugRescue Medications

    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.

Outcome measures

Primary

  • Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

    DLT will be defined as any drug-related AE observed during the DLT evaluation period (up to 42 days) that results in a change to a given dose or a delay in initiating the next treatment.

    Time frame: Up to 42 days

  • Number of Participants Who Experience an Adverse Event (AE)

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.

    Time frame: Up to approximately 65 months

  • Number of Participants Who Discontinue Study Treatment Due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinue study intervention due to an AE will be reported.

    Time frame: Up to approximately 64 months

  • Objective Response Rate (ORR)

    ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

    Time frame: Up to approximately 65 months

Secondary

  • Duration of Response (DOR)

    Time frame: Up to approximately 65 months

  • Progression-Free Survival (PFS)

    Time frame: Up to approximately 124 months

  • Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC tau)

    Time frame: Predose and at designated time points post-dose (up to approximately 65 months)

  • Maximum Plasma Concentration (Cmax)

    Time frame: Predose and at designated time points post-dose (up to approximately 65 months)

  • Minimum Observed Concentration (Ctrough)

    Time frame: Predose and at designated time points post-dose (up to approximately 65 months)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 * 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 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 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

Study locations (4)

Clermont Oncology Center ( Site 0041)

Clermont, Florida, 34711

Recruiting
Study Coordinator · Contact

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

Chicago, Illinois, 60612

Recruiting
Study Coordinator · Contact

Providence Portland Medical Center ( Site 0043)

Portland, Oregon, 97213

Recruiting
Study Coordinator · Contact

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

Portland, Oregon, 97225

Recruiting
Study Coordinator · Contact