KEYMAKER-U01 Substudy 01J: A Study of Pembrolizumab Plus MK-1084 in Participants With Non-Small Cell Lung Cancer (NSCLC) With Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) G12C Mutations (MK-3475-01J/KEYMAKER-U01J)

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• 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

You cannot join if

• 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

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

Kras G12C inhibitor MK-1084. An orally available inhibitor of the oncogenic KRAS substitution mutation G12C, with potential antineoplastic activity. Upon oral administration, KRAS G12C inhibitor MK-1084 selectively targets the KRAS G12C mutant and inhibits KRAS G12C-mediated signaling. This may halt proliferation and metastasis in susceptible tumor cells. KRAS, a member of the RAS family of oncogenes, serves an important role in cell signaling, division and differentiation. Mutations of KRAS may induce constitutive signal transduction leading to tumor cell proliferation, invasion, and metastasis. NCI Drug Dictionary

pembrolizumab. A humanized monoclonal immunoglobulin (Ig) G4 antibody directed against human cell surface receptor PD-1 (programmed death-1 or programmed cell death-1) with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, pembrolizumab binds to PD-1, an inhibitory signaling receptor expressed on the surface of activated T cells, and blocks the binding to and activation of PD-1 by its ligands, which results in the activation of T-cell-mediated immune responses against tumor cells. The ligands for PD-1 include programmed cell death ligand 1 (PD-L1), overexpressed on certain cancer cells, and programmed cell death ligand 2 (PD-L2), which is primarily expressed on APCs. Activated PD-1 negatively regulates T-cell activation and plays a key role in in tumor evasion from host immunity. NCI Drug Dictionary

Treatments listed in the registry

• MK-1084 (Drug): Oral Administration
• Pembrolizumab (Biological): Intravenous administration
• Cetuximab (Biological): Intravenous administration
• Sacituzumab tirumotecan (sac-TMT) (Biological): Injection powder for intravenous infusion
• Rescue medication (Drug): 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.

Randomized · Parallel · masking: Single

Main goals

• Percentage of Participants with a Dose Limiting Toxicity (DLT) (Up to approximately 21 days)
• Percentage of Participants who Experience at Least One Adverse Event (AE) (Up to approximately 84 months)
• Percentage of Participants who Discontinue Study Intervention Due to an AE (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) (Up to approximately 84 months)

Other goals

• Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
• Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR
• Overall Survival (OS)
• Area Under the Concentration-Time Curve (AUC) for MK-1084
• Maximum Concentration (Cmax) of MK-1084
• Trough Concentration (Ctrough) of MK-1084

Planned enrollment: 140 (estimated).

• Clermont Oncology Center ( Site 0041), Clermont, Florida
• Sanford Health Roger Maris Cancer Center ( Site 0039), Fargo, North Dakota
• Sanford Cancer Center Oncology Clinic ( Site 0038), Sioux Falls, South Dakota

35 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07252739
• NCI Drug Dictionary: C185288
• NCI Drug Dictionary: C106432

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 1, 2026. Public record; not medical advice.