Recruiting
Phase 2

MK-1084

Sponsor:

Merck Sharp & Dohme LLC

Code:

NCT07252739

Conditions

Malignant Neoplasm

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

MK-1084

Pembrolizumab

Cetuximab

Sacituzumab tirumotecan (sac-TMT)

Rescue medication

Study Details

Brief summary:

Researchers want to learn if using a study medicine called MK-1084 can help treat Non-Small Cell Lung Cancer (NSCLC). MK-1084 is a type of treatment called targeted therapy for the Kirsten rat sarcoma viral oncogene homolog (KRAS) G12C gene change. The goal of this study is to learn about the safety of MK-1084 and to learn how many people have the cancer get smaller or go away during the study treatment.

Conditions

Malignant Neoplasm

Study ID

NCT07252739

Start date

Dec 19, 2025

Status verified date

Sep, 2026

Completion date

May 31, 2032

Anticipated

Primary completion date

Nov 15, 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 nonsquamous 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 homolog (KRAS) G12C mutations
  • Can provide an archival tumor tissue sample or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated
  • Has recovered to ≤Grade 1 or baseline from any Adverse events (AEs) due to previous anticancer therapies and/or ≤Grade 2 neuropathy and/or endocrine-related AEs adequately treated with hormone replacement
  • Has well controlled human immunodeficiency virus (HIV) on antiretroviral therapy (ART) if HIV-infected
  • Has undetectable hepatitis B (HBV) viral load and have received HBV antiviral therapy for at least 4 weeks if hepatitis B surface antigen (HBsAg) positive
  • Has undetectable hepatitis C (HCV) viral load if HCV-infected

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 HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
  • Has uncontrolled, clinically significant cardiovascular disease or cerebrovascular disease, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of corrected QT interval corrected for heart rate by Fridericia's formula (QTcF) interval to >470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
  • Has received prior systemic anticancer therapy for advanced or metastatic NSCLC
  • Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher immune-related adverse event (irAE) (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis
  • Has received previous treatment with an agent targeting KRAS
  • Has received prior systemic anticancer therapy within 4 weeks or 5 half-lives (whichever is shorter) and has not recovered to grade ≤ 1 or baseline from AE associated with anticancer therapy before allocation/randomization
  • Has received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has a known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed
  • Has a history of (noninfectious) pneumonitis/interstitial lung disease (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at screening
  • Has a history of stem cell/solid organ transplant
  • Has not adequately recovered from major surgery or has ongoing surgical complications

Study Design

Enrollment

140 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A- Pembrolizumab + MK-1084

Participants receive 400 mg of Pembrolizumab every 6 weeks and MK-1084 dose regimen.

experimental: Arm B- Pembrolizumab + MK-1084 + Cetuximab

Participants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and Cetuximab 500 mg/m\^2 every 2 weeks.

experimental: Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)

Participants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and 4 mg/kg sacituzumab tirumotecan (sac-TMT) every 2 weeks.

Interventions

MK-1084

Oral Administration

Pembrolizumab

Intravenous administration

Cetuximab

Intravenous administration

Sacituzumab tirumotecan (sac-TMT)

Injection powder for intravenous infusion

Rescue medication

Participants receive the following rescue medications, per approved product label, as premedication to study treatment to prevent hypersensitivity and/or infusion reactions: diphenhydramine (or equivalent histamine-1 \[Hl\] receptor antagonist), H2 receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, and granulocyte colony-stimulating factor (G-CSF). A steroid mouthwash (dexamethasone or equivalent) will be given as prophylaxis for stomatitis/oral mucositis.

Primary outcome measure

  • Percentage of Participants with a Dose Limiting Toxicity (DLT) [ Time Frame: Up to approximately 21 days ]
  • Percentage of Participants who Experience at Least One Adverse Event (AE) [ Time Frame: Up to approximately 84 months ]
  • Percentage of Participants who Discontinue Study Intervention Due to an AE [ Time Frame: Up to approximately 84 months ]
  • Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 84 months ]

Central Contacts and Locations

Central contacts

Locations

Clermont Oncology Center ( Site 0041)

Recruiting

Clermont, Florida, United States, 34711

Contacts

Study Coordinator

386-538-3169

Sanford Health Roger Maris Cancer Center ( Site 0039)

Recruiting

Fargo, North Dakota, United States, 58102

Contacts

Study Coordinator

701-234-2000

Sanford Cancer Center Oncology Clinic ( Site 0038)

Recruiting

Sioux Falls, South Dakota, United States, 57104

Contacts

Study Coordinator

605-328-8000

More Information

Sponsor

Merck Sharp & Dohme LLC

Last update posted

Sep 2, 2026

Last verified

Sep, 2026

Keywords

  • Programmed Cell Death-1 (PD1, PD-1)
  • Programmed Cell Death 1 Ligand 1 (PDL1, PD-L1)
  • Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-08. This information was provided to ClinicalTrials.gov by Merck Sharp & Dohme LLC on 2026-09-02. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.