Recruiting
Phase 1
Phase 2

MK-1084

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT07286149

Conditions

Lung Neoplasm Malignant

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

MK-1084

Patritumab deruxtecan

Sacituzumab tirumotecan

Cetuximab

Rescue Medications

Study Details

Brief 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

Conditions

Lung Neoplasm Malignant

Study ID

NCT07286149

Start date

Apr 30, 2026

Status verified date

Sep, 2026

Completion date

Apr 13, 2032

Anticipated

Primary completion date

Aug 17, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

140 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: MK-1084 + Cetuximab

Participants will receive MK-1084 and cetuximab until discontinuation due to toxicity, AE or at the discretion of an investigator. Per amendment 3, the MK-1084 + Cetuximab arm was discontinued.

Interventions

MK-1084

Oral administration

Patritumab deruxtecan

IV infusion

Sacituzumab tirumotecan

IV Infusion

Cetuximab

IV Infusion

Rescue Medications

Participants receive rescue medication at the investigator's discretion for prevention of nausea and vomiting, per approved product label. Recommended rescue medications are histamine-1 (H1) receptor antagonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent), 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, neurokinin 1 (NK-1) receptor antagonist and corticosteroid.

Primary outcome measure

  • Number of Participants Who Experience a Dose Limiting Toxicity (DLT) [ Time Frame: Up to 42 days ]
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Up to approximately 63 months ]
  • Number of Participants Who Discontinue Study Treatment Due to an AE [ Time Frame: Up to approximately 62 months ]
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 63 months ]

Central Contacts and Locations

Central contacts

Toll Free Number

1-888-577-8839Trialsites@msd.com

Locations

Clermont Oncology Center ( Site 0041)

Recruiting

Clermont, Florida, United States, 34711

Contacts

Study Coordinator

386-538-3169

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

Recruiting

Chicago, Illinois, United States, 60612

Contacts

Study Coordinator

312-996-9272

Providence Portland Medical Center ( Site 0043)

Recruiting

Portland, Oregon, United States, 97213

Contacts

Study Coordinator

503-215-1979

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

Recruiting

Portland, Oregon, United States, 97225

Contacts

Study Coordinator

503-215-1979

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 2, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-02.