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Malignant NeoplasmPhase 2NCT07252739

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)

A Phase 2 study testing MK-1084, Pembrolizumab and Cetuximab in people with Malignant Neoplasm, run by Merck Sharp & Dohme LLC at 39 sites in 13 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Malignant Neoplasm
What is being tested?
MK-1084, Pembrolizumab and Cetuximab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
39 sitesin 13 countries
Study dates
19 Dec 2025to 31 May 2032
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

39 sites in 13 countries. Contact the study team or a site near you to ask about taking part.

Toll Free Number contact

1-888-577-8839

Trialsites@msd.com

39 sites in 13 countries

Ukraine9 sites, 8 recruiting

  • COMMUNAL NONPROFIT ENTERPRISE CLINICAL CENTER OF ONCOLOGY, HEMATOLOGY, TRANSPLANTOLOGY AND PALLIATI ( Site 0139)

    Cherkasy, Cherkasy Oblast, 18009

    Study Coordinator, +380472370123

    Recruiting

  • Communal Non-Commercial Enterprise "Prykarpatski Clinical On-Surgery department #2 ( Site 0132)

    Ivano-Frankivsk, Ivano-Frankivsk Oblast, 76018

    Study Coordinator, 380978411455

    Recruiting

  • Limited Liability Company Ukrainian Center of Tomotherapy-Department of Chemotherapy ( Site 0467)

    Kropyvnytskyi, Kirovohrad Oblast, 25011

    Study Coordinator, +380958718674

    Recruiting

  • Medical Center "Mriya Med-Service"-Clinical Research Department ( Site 0465)

    Kryvyi Rih, Dnipropetrovsk Oblast, 50000

    Study Coordinator, +380677490687

    Recruiting

  • VISION PARTNER Medical Centre ( Site 0135)

    Kyiv, 03022

    Active, not recruiting

  • LIMITED LIABILITY COMPANY "MEDICAL CENTER "DOBROBUT-CLINIC" ( Site 0138)

    Kyiv, 03151

    Study Coordinator, +380671502987

    Recruiting

  • Lviv Territorial Medical Union Multidisciplinary Clinical Hospital ( Site 0133)

    Lviv, Lviv Oblast, 79059

    Study Coordinator, +380677724757

    Recruiting

  • Uzhhorod Municipal Multidisciplinary Clinical Hospital of Uzhhorod City Council ( Site 0137)

    Uzhhorod, Zakarpattia Oblast, 88000

    Study Coordinator, +380506847086

    Recruiting

  • Communal Noncommercial Enterprise "Podillia Regional Oncolog-Cardiothoracic department ( Site 0131)

    Vinnitsya, Vinnytsia Oblast, 21029

    Study Coordinator, 380953105783

    Recruiting

Other trials in Ukraine

Turkey (Türkiye)5 sites, 5 recruiting

  • Baskent University Dr. Turgut Noyan Research and Training Center ( Site 0141)

    Adana, 1250

    Study Coordinator, +905537766235

    Recruiting

  • Koç Üniversitesi Hastanesi ( Site 0142)

    Adana, 34010

    Study Coordinator, 08502508250-21251

    Recruiting

  • Liv Hospital Ankara ( Site 0146)

    Ankara, 06680

    Study Coordinator, 905469299990

    Recruiting

  • Hacettepe Universite Hastaneleri ( Site 0140)

    Ankara, 6230

    Study Coordinator, +90 312 305 50 00

    Recruiting

  • Erciyes University ( Site 0145)

    Talas, Kayseri, 38039

    Study Coordinator, 905366550924

    Recruiting

Other trials in Turkey (Türkiye)

China4 sites, 4 recruiting

  • West China Hospital, Sichuan University ( Site 0315)

    Chengdu, Sichuan, 610066

    Study Coordinator, +8618980602252

    Recruiting

  • The First affiliated hospital of Nanchang University (Xianghu campus) ( Site 0306)

    Nanchang, Jiangxi, 330209

    Study Coordinator, +86 791 8631 9333

    Recruiting

  • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School ( Site 0318)

    Nanjing, Jiangsu, 210000

    Study Coordinator, +8602568182222

    Recruiting

  • Zhongshan Hospital Fudan University ( Site 0319)

    Shanghai, Shanghai Municipality, 200032

    Study Coordinator, +8615000229853

    Recruiting

Other trials in China

Finland4 sites, 4 recruiting

  • HYKS Syöpätautien klinikka ( Site 0260)

    Helsinki, Uusimaa, 00290

    Study Coordinator, +358406682951

    Recruiting

  • Kuopion Yliopistollinen Sairaala ( Site 0261)

    Kuopio, Northern Savonia, 70200

    Study Coordinator, +35817173311

    Recruiting

  • Turku University Hospital ( Site 0262)

    Turku, Southwest Finland, 20520

    Study Coordinator, +35823138709

    Recruiting

  • Vaasan Keskussairaala ( Site 0263)

    Vaasa, Pohjanmaa, 65130

    Study Coordinator, +358405533545

    Recruiting

Other trials in Finland

United States3 sites, 3 recruiting

  • Clermont Oncology Center ( Site 0041)

    Clermont, Florida, 34711

    Study Coordinator, 386-538-3169

    Recruiting

  • Sanford Health Roger Maris Cancer Center ( Site 0039)

    Fargo, North Dakota, 58102

    Study Coordinator, 701-234-2000

    Recruiting

  • Sanford Cancer Center Oncology Clinic ( Site 0038)

    Sioux Falls, South Dakota, 57104

    Study Coordinator, 605-328-8000

    Recruiting

Other trials in United States

Chile3 sites, 3 recruiting

  • Fundacion Arturo Lopez Perez ( Site 0167)

    Santiago, Region M. de Santiago, 7500921

    Study Coordinator, 56224205098

    Recruiting

  • Centro de Oncología de Precisión ( Site 0160)

    Santiago, Region M. de Santiago, 7560908

    Study Coordinator, +56991612199

    Recruiting

  • Bradfordhill ( Site 0168)

    Santiago, Region M. de Santiago, 8420383

    Study Coordinator, +56998744662

    Recruiting

Other trials in Chile

Hong Kong3 sites, 3 recruiting

  • Hong Kong Integrated Oncology Centre ( Site 0232)

    Central, 0000

    Study Coordinator, +85237006888

    Recruiting

  • Queen Mary Hospital ( Site 0230)

    Hong Kong

    Study Coordinator, +85222551727

    Recruiting

  • Hong Kong United Oncology Centre ( Site 0231)

    Kowloon

    Study Coordinator, +852 2386 8002

    Recruiting

Other trials in Hong Kong

Netherlands2 sites, 2 recruiting

  • Deventer Ziekenhuis ( Site 0272)

    Deventer, Overijssel, 7416 SE

    Study Coordinator, +31570536437

    Recruiting

  • Leids Universitair Medisch Centrum ( Site 0273)

    Leiden, South Holland, 2333 ZA

    Study Coordinator, +31715566376

    Recruiting

Other trials in Netherlands

Thailand2 sites, 2 recruiting

  • Bangkok Metropolitan Administration Medical College and Vajira Hospital ( Site 0351)

    Bangkok, Bangkok, 10300

    Study Coordinator, +6622443461

    Recruiting

  • Faculty of Medicine Siriraj Hospital ( Site 0350)

    Bangkok, Bangkok, 10700

    Study Coordinator, +6624194488-9

    Recruiting

Other trials in Thailand

Greece1 site, 1 recruiting

  • Evangelismos General Hospital of Athens ( Site 0200)

    Athens, Attica, 106 76

    Study Coordinator, +302132041631

    Recruiting

Other trials in Greece

Italy1 site, 1 recruiting

  • Fondazione IRCCS Istituto Nazionale Dei Tumori ( Site 0175)

    Milan, Lombardy, 20133

    Study Coordinator, 00390223903829

    Recruiting

Other trials in Italy

South Korea1 site, 1 recruiting

  • Severance Hospital Yonsei University Health System ( Site 0080)

    Seoul, 03722

    Study Coordinator, +82222280880

    Recruiting

Other trials in South Korea

Spain1 site, 1 recruiting

  • Hospital Universitario Virgen de la Macarena ( Site 0093)

    Seville, 41009

    Study Coordinator, +34 671560092

    Recruiting

Other trials in Spain

About this study

Official title: KEYMAKER-U01 Substudy 01J: A Randomized Phase 2 Umbrella Study With Rolling Arms of Investigational Agents for First-line Treatment of Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations

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.

Being tested
MK-1084, Pembrolizumab, Cetuximab, Sacituzumab tirumotecan (sac-TMT), Rescue medication
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)
Medical subject headings
Neoplasms, Parkinson Disease 4, Autosomal Dominant Lewy Body

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-1084Drug

    Oral Administration

  • PembrolizumabBiological

    Also called Keytruda, MK-3475

    Intravenous administration

  • CetuximabBiological

    Intravenous administration

  • Sacituzumab tirumotecan (sac-TMT)Biological

    Also called MK-2870, SKB264

    Injection powder for intravenous infusion

  • Rescue medicationDrug

    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.

Study groups in NCT07252739
Study groupRoleWhat they receive
Arm A- Pembrolizumab + MK-1084ExperimentalParticipants receive 400 mg of Pembrolizumab every 6 weeks and MK-1084 dose regimen.
Receives: Drug: MK-1084; Biological: Pembrolizumab
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.
Receives: Drug: MK-1084; Biological: Pembrolizumab; Biological: Cetuximab
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.
Receives: Drug: MK-1084; Biological: Pembrolizumab; Biological: Sacituzumab tirumotecan (sac-TMT); Drug: Rescue medication

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants with a Dose Limiting Toxicity (DLT)

    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.

    Measured: Up to approximately 21 days

  2. Percentage of Participants who Experience at Least One Adverse Event (AE)

    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.

    Measured: Up to approximately 84 months

  3. Percentage of Participants who Discontinue Study Intervention Due to an AE

    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.

    Measured: Up to approximately 84 months

  4. Objective Response Rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 as assessed by Blinded Independent Central Review (BICR)

    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.

    Measured: Up to approximately 84 months

Secondary outcomes (6)

  1. Duration of Response (DOR) per RECIST 1.1 as assessed by BICR

    For participants who demonstrate a confirmed 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, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.

    Measured: Up to approximately 84 months

  2. Progression Free Survival (PFS) per RECIST 1.1 as assessed by BICR

    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by BICR will be presented.

    Measured: Up to approximately 84 months

  3. Overall Survival (OS)

    OS, defined as the time from first dose or randomization (depending on study period) to death due to any cause. OS will be presented.

    Measured: Up to approximately 84 months

  4. Area Under the Concentration-Time Curve (AUC) for MK-1084

    Blood samples will be collected to determine the AUC of MK-1084.

    Measured: At designated timepoints (up to approximately 44 days)

  5. Maximum Concentration (Cmax) of MK-1084

    Blood samples will be collected to estimate Cmax of MK-1084.

    Measured: At designated timepoints (up to approximately 44 days)

  6. Trough Concentration (Ctrough) of MK-1084

    Blood samples will be collected to determine the Ctrough of MK-1084.

    Measured: At designated timepoints (up to approximately 84 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Nov 2025
  2. Study start19 Dec 2025
  3. Primary completion15 Nov 2029 (estimated)
  4. Study completion31 May 2032 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07252739
Sponsor's protocol ID
3475-01J
Other IDs
U1111-1321-3999, 2025-521939-36-00, 2025
Status last verified
Sep 2026
First submitted
20 Nov 2025
Last updated
2 Sep 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MK-1084, Pembrolizumab and Cetuximab in people with Malignant Neoplasm, run by Merck Sharp & Dohme LLC at 39 sites in 13 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 2 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 sites in Ukraine, Turkey (Türkiye), China, Finland, United States and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Toll Free Number (1-888-577-8839, Trialsites@msd.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants with a Dose Limiting Toxicity (DLT) (time frame: Up to approximately 21 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07252739.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2026.

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