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MK-1084

Phase 2

Malignant Neoplasm | Small molecule | Oncology |Merck & Company, Inc.|Last Updated: Aug 6, 2026

Target and mechanism

Molecular targetKRAS G12C
ModalitySmall molecule

Success Probability

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Market & Valuation

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Trial Design

RandomizedCONTROLLED
Total Trials1
Total Enrollment140

FDA Designations

No designations recorded

Clinical trial landscape

MK-1084 · 2 trials · 2 indications

Phase 2 1Phase 1 1
NCT07252739KEYMAKER-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)Malignant Neoplasm
RECRUITING140 Analytics
PHASE2RECRUITING
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)
Malignant NeoplasmUnlock trial analytics

Study Endpoints

Primary Endpoints

Percentage of Participants with a Dose Limiting Toxicity (DLT)
Up to approximately 21 days

A DLT is defined as the occurrence of protocol-specified toxicities if assessed by the investigator to be possibly, probably, or definitely related to study intervention administration, excluding toxicities clearly not related to the drug.

Percentage of Participants who Experience at Least One Adverse Event (AE)
Up to approximately 84 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Percentage of Participants who Discontinue Study Intervention Due to an AE
Up to approximately 84 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

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

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.

Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
Up to 42 days

DLT will be defined as any drug-related AE observed during the DLT evaluation period (up to 42 days) that results in a change to a given dose or a delay in initiating the next treatment.

Number of Participants Who Experience an Adverse Event (AE)
Up to approximately 63 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.

Number of Participants Who Discontinue Study Treatment Due to an AE
Up to approximately 62 months

An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinue study intervention due to an AE will be reported.

Objective Response Rate (ORR)
Up to approximately 63 months

ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.

Secondary Endpoints

Duration of Response (DOR) per RECIST 1.1 as assessed by BICR
Up to approximately 84 months
Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR
Up to approximately 84 months
Overall Survival (OS)
Up to approximately 84 months
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Study Design & Arms

AllocationRANDOMIZED
MaskingSINGLE
ModelPARALLEL
PurposeTREATMENT

Treatment Arms

ArmTypeDescription
Arm A- Pembrolizumab + MK-1084EXPERIMENTALParticipants receive 400 mg of Pembrolizumab every 6 weeks and MK-1084 dose regimen.
Arm B- Pembrolizumab + MK-1084 + CetuximabEXPERIMENTALParticipants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and Cetuximab 500 mg/m\^2 every 2 weeks.
Arm C- Pembrolizumab + MK-1084 + sacituzumab tirumotecan (sac-TMT)EXPERIMENTALParticipants receive 400 mg of Pembrolizumab every 6 weeks, MK-1084 dose regimen, and 4 mg/kg sacituzumab tirumotecan (sac-TMT) every 2 weeks.
MK-1084 + Patritumab deruxtecan (HER3-DXd)EXPERIMENTALParticipants will receive MK-1084 and HER3-DXd until discontinuation due to toxicity, adverse event (AE) or at the discretion of an investigator.
MK-1084 + Sacituzumab tirumotecan (Sac-TMT)EXPERIMENTALParticipants will receive MK-1084 and sac-TMT until discontinuation due to toxicity, AE or at the discretion of an investigator.
MK-1084 + CetuximabEXPERIMENTALParticipants 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

NameTypeDescription
MK-1084DRUGOral Administration
PembrolizumabBIOLOGICALIntravenous administration
CetuximabBIOLOGICALIntravenous administration
Sacituzumab tirumotecan (sac-TMT)BIOLOGICALInjection powder for intravenous infusion
Rescue medicationDRUGParticipants 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.
Patritumab deruxtecanBIOLOGICALIV infusion
Sacituzumab tirumotecanBIOLOGICALIV Infusion
Rescue MedicationsDRUGParticipants 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.
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Eligibility Criteria

Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites38

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) tha...

Countries:United StatesChileChinaFinlandGreeceHong KongItalyNetherlandsSouth KoreaSpainThailandTurkey (Türkiye)UkraineBrazilGermanyIsrael
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Recent Changes (Last 90 Days)

LOWAug 6, 2026NCT07286149lastUpdatePostDate: changed
LOWAug 6, 2026NCT07286149lastUpdatePostDate: changed
LOWJul 30, 2026NCT07252739lastUpdatePostDate: changed
LOWJul 30, 2026NCT07252739lastUpdatePostDate: changed
MEDIUMJul 29, 2026NCT07252739Enrollment: 130 → 140
MEDIUMJul 29, 2026NCT07252739Enrollment: 130 → 140
HIGHJul 22, 2026NCT07286149Enrollment: 190 → 140
HIGHJul 22, 2026NCT07286149Enrollment: 190 → 140
LOWJul 10, 2026NCT07252739lastUpdatePostDate: changed
LOWJul 10, 2026NCT07252739lastUpdatePostDate: changed
LOWJun 26, 2026NCT07252739lastUpdatePostDate: changed
LOWJun 26, 2026NCT07252739lastUpdatePostDate: changed
LOWJun 23, 2026NCT07252739lastUpdatePostDate: changed
LOWJun 23, 2026NCT07252739lastUpdatePostDate: changed
LOWJun 18, 2026NCT07286149lastUpdatePostDate: changed
LOWJun 18, 2026NCT07286149lastUpdatePostDate: changed
LOWJun 18, 2026NCT07286149lastUpdatePostDate: changed
LOWJun 12, 2026NCT07252739lastUpdatePostDate: changed
LOWJun 12, 2026NCT07286149Completion: 2037-05-06 → 2032-04-13
LOWJun 12, 2026NCT07252739lastUpdatePostDate: changed

Frequently asked questions about MK-1084

What is MK-1084 used for?

MK-1084 is an investigational small molecule being studied for the treatment of malignant neoplasms, including non-small cell lung cancer (NSCLC) with KRAS G12C mutations. It is currently in Phase 1 and Phase 2 clinical trials as part of combination therapy regimens for these cancers.

What does MK-1084 target?

MK-1084 targets KRAS G12C, a specific mutation in the KRAS gene associated with certain cancers, including non-small cell lung cancer. By targeting this mutation, MK-1084 is designed to interfere with cancer cell growth and survival in tumors harboring the KRAS G12C alteration.

Who makes MK-1084?

MK-1084 is being developed by Merck & Company, Inc., a pharmaceutical company traded on the New York Stock Exchange under the ticker symbol MRK. Merck is conducting clinical trials to evaluate MK-1084 in combination with other treatments for KRAS G12C-mutated cancers.

What phase is MK-1084 in?

MK-1084 is in Phase 1 and Phase 2 clinical development. It is an investigational drug, not yet approved by regulatory authorities, and is being studied in combination with other therapies for non-small cell lung cancer and other malignant neoplasms.

What clinical trials is MK-1084 in?

MK-1084 is being studied in two recruiting trials. NCT07252739 is a Phase 2 study of pembrolizumab plus MK-1084 in NSCLC with KRAS G12C mutations. NCT07286149 is a Phase 1 study of MK-1084 with other treatments for NSCLC. Both trials enroll adults aged 18 and older.

Is MK-1084 the same as pembrolizumab?

No, MK-1084 is not the same as pembrolizumab. MK-1084 is a small molecule targeting KRAS G12C, while pembrolizumab is an immunotherapy that targets PD-1. In clinical trials, MK-1084 is being studied in combination with pembrolizumab for the treatment of KRAS G12C-mutated non-small cell lung cancer.