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

NCT ID: NCT07286149

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-02-23

Study Completion Date

2036-07-20

Brief Summary

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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

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This is a substudy of the master protocol MK-3475-U01 (KEYMAKER-U01) - NCT04165798.

Conditions

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Lung Neoplasm Malignant

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Participants will be enrolled and treated sequentially during dose escalation followed by parallel assignment in the expansion phase.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MK-1084 + Patritumab deruxtecan (HER3-DXd)

Participants will receive MK-1084 and HER3-DXd until discontinuation due to toxicity, adverse event (AE) or at the discretion of an investigator.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral administration

Patritumab deruxtecan

Intervention Type BIOLOGICAL

IV infusion

MK-1084 + Sacituzumab tirumotecan (Sac-TMT)

Participants will receive MK-1084 and sac-TMT until discontinuation due to toxicity, AE or at the discretion of an investigator.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral administration

Sacituzumab tirumotecan

Intervention Type BIOLOGICAL

IV Infusion

Rescue Medications

Intervention Type DRUG

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.

MK-1084 + Cetuximab

Participants will receive MK-1084 and cetuximab until discontinuation due to toxicity, AE or at the discretion of an investigator.

Group Type EXPERIMENTAL

MK-1084

Intervention Type DRUG

Oral administration

Cetuximab

Intervention Type BIOLOGICAL

IV Infusion

Interventions

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MK-1084

Oral administration

Intervention Type DRUG

Patritumab deruxtecan

IV infusion

Intervention Type BIOLOGICAL

Sacituzumab tirumotecan

IV Infusion

Intervention Type BIOLOGICAL

Cetuximab

IV Infusion

Intervention Type BIOLOGICAL

Rescue 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.

Intervention Type DRUG

Other Intervention Names

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HER3-DXd MK-1022 U3-1402 Sac-TMT MK-2870 SKB264 C225 Erbitux

Eligibility Criteria

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Inclusion Criteria

* 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

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Daiichi Sankyo

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Related Links

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http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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MK-3475-01F

Identifier Type: OTHER

Identifier Source: secondary_id

2024-512248-47-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1304-4707

Identifier Type: REGISTRY

Identifier Source: secondary_id

3475-01F

Identifier Type: -

Identifier Source: org_study_id