Purpose

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.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy 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 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

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Single (Outcomes Assessor)
Masking Description
Some outcome measures will be assessed by blinded independent central review (BICR), with assessor(s) blinded to intervention assignment.

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm A- Pembrolizumab + MK-1084
Participants receive 400 mg of Pembrolizumab every 6 weeks and MK-1084 dose regimen.
  • Drug: MK-1084
    Oral Administration
  • Biological: Pembrolizumab
    Intravenous administration
    Other names:
    • Keytruda
    • MK-3475
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.
  • Drug: MK-1084
    Oral Administration
  • Biological: Pembrolizumab
    Intravenous administration
    Other names:
    • Keytruda
    • MK-3475
  • Biological: Cetuximab
    Intravenous administration
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.
  • Drug: MK-1084
    Oral Administration
  • Biological: Pembrolizumab
    Intravenous administration
    Other names:
    • Keytruda
    • MK-3475
  • Biological: Sacituzumab tirumotecan (sac-TMT)
    Injection powder for intravenous infusion
    Other names:
    • MK-2870
    • SKB264
  • Drug: 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.

Recruiting Locations

Clermont Oncology Center ( Site 0041)
Clermont, Florida 34711
Contact:
Study Coordinator
386-538-3169

Sanford Health Roger Maris Cancer Center ( Site 0039)
Fargo, North Dakota 58102
Contact:
Study Coordinator
701-234-2000

Sanford Cancer Center Oncology Clinic ( Site 0038)
Sioux Falls, South Dakota 57104
Contact:
Study Coordinator
605-328-8000

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Toll Free Number
1-888-577-8839
Trialsites@msd.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.