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Lung Neoplasm MalignantPhase 1/2NCT07286149

A Clinical Study of MK-1084 With Other Treatments for Non-small Cell Lung Cancer (MK-3475-01F)

A Phase 1/2 study testing MK-1084, Patritumab deruxtecan and Sacituzumab tirumotecan in people with Lung Neoplasm Malignant, run by Merck Sharp & Dohme LLC at 29 sites in 11 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 MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lung Neoplasm Malignant
What is being tested?
MK-1084, Patritumab deruxtecan and Sacituzumab tirumotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
140 participants
Where
29 sitesin 11 countries
Study dates
30 Apr 2026to 13 Apr 2032
Phase
Phase 1/2
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 non-squamous 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 (KRAS) mutation of glycine to cysteine at codon 12 (G12C) mutations
  • Has documented disease progression after receiving 1-2 prior lines of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy and platinum-based chemotherapy
  • Has provided tumor tissue for biomarker analysis from an archival sample or a newly obtained core or excisional biopsy of a tumor lesion not previously irradiated
  • Participants with human immunodeficiency virus (HIV) infection must have well-controlled HIV on antiretroviral therapy (ART) per protocol

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 clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses
  • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
  • Has active inflammatory bowel disease requiring immunosuppressive medication or previous history of inflammatory bowel disease
  • Has evidence of any leptomeningeal disease
Show all 15Show fewer
  • Has uncontrolled or significant cardiovascular disorder or cerebrovascular disease prior to allocation/randomization
  • Has one or more of the following ophthalmological conditions: a) Clinically significant corneal disease b) history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis
  • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
  • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
  • Has known additional malignancy that is progressing or has required active treatment within the past 3 years
  • Has any history of interstitial lung disease (ILD)/pneumonitis irrespective of steroid use or current ILD, or suspected ILD
  • Has an active infection requiring systemic therapy
  • Has not adequately recovered from major surgery or has ongoing surgical complications

Trial locations and contacts

29 sites in 11 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

29 sites in 11 countries

United States4 sites, 4 recruiting

  • University of Illinois Hospital & Health Sciences System ( Site 0044)

    Chicago, Illinois, 60612

    Study Coordinator, 312-996-9272

    Recruiting

  • Clermont Oncology Center ( Site 0041)

    Clermont, Florida, 34711

    Study Coordinator, 386-538-3169

    Recruiting

  • Providence Portland Medical Center ( Site 0043)

    Portland, Oregon, 97213

    Study Coordinator, 503-215-1979

    Recruiting

  • Providence Oncology and Hematology Care Clinic - Westside ( Site 0059)

    Portland, Oregon, 97225

    Study Coordinator, 503-215-1979

    Recruiting

Other trials in United States

Brazil4 sites, 4 recruiting

  • Fundação Pio XII - Hospital de Câncer de Barretos ( Site 0282)

    Barretos, São Paulo, 14784-400

    Study Coordinator, +551733216637

    Recruiting

  • Hospital São Lucas da PUCRS ( Site 0283)

    Porto Alegre, Rio Grande do Sul, 90610-000

    Study Coordinator, +555133203000

    Recruiting

  • Fundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0286)

    São José do Rio Preto, São Paulo, 15090-000

    Study Coordinator, +551732015000

    Recruiting

  • Hospital Paulistano ( Site 0280)

    São Paulo, São Paulo, 01321001

    Study Coordinator, 55 11 31411083

    Recruiting

Other trials in Brazil

Spain4 sites, 4 recruiting

  • Hospital Clinic de Barcelona ( Site 0092)

    Barcelona, 08036

    Study Coordinator, 34 932275402

    Recruiting

  • Institut Català d'Oncologia - L'Hospitalet ( Site 0090)

    Hospitalet, Barcelona, 08908

    Study Coordinator, 0034932607744

    Recruiting

  • HOSPITAL UNIVERSITARIO QUIRONSALUD MADRID ( Site 0091)

    Pozuelo de Alarcón, Madrid, 28223

    Study Coordinator, +34914521987

    Recruiting

  • Hospital Universitario Virgen Macarena ( Site 0093)

    Seville, 41009

    Study Coordinator, +34 671560092

    Recruiting

Other trials in Spain

Chile3 sites, 3 recruiting

  • Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0162)

    Santiago, Region M. de Santiago, 7500653

    Study Coordinator, +56991612199

    Recruiting

  • Fundación Arturo López Pérez ( Site 0161)

    Santiago, Region M. de Santiago, 7500921

    Study Coordinator, 56229490970

    Recruiting

  • Bradfordhill ( Site 0160)

    Santiago, Region M. de Santiago, 8420383

    Study Coordinator, +56229490970

    Recruiting

Other trials in Chile

Greece3 sites, 3 recruiting

  • THORACIC GENERAL HOSPITAL OF ATHENS "I SOTIRIA" ( Site 0204)

    Athens, Attica, 115 27

    Study Coordinator, +30210 7763100

    Recruiting

  • Alexandra General Hospital of Athens-ONCOLOGY DEPT. ( Site 0205)

    Athens, Attica, 115 28

    Study Coordinator, +302132162543

    Recruiting

  • Papageorgiou General Hospital of Thessaloniki ( Site 0206)

    N.Efkarpia, Thessaloniki, 564 29

    Study Coordinator, +302313323959

    Recruiting

Other trials in Greece

Hong Kong3 sites, 3 recruiting

  • Queen Mary Hospital ( Site 0230)

    Hong Kong, 000000

    Study Coordinator, +85222551727

    Recruiting

  • Hong Kong United Oncology Centre ( Site 0232)

    Jordan, 000000

    Study Coordinator, +852 5508 7858

    Recruiting

  • Prince of Wales Hospital ( Site 0231)

    Shatin

    Study Coordinator, +852 3505 1202

    Recruiting

Other trials in Hong Kong

Israel3 sites, 3 recruiting

  • Shaare Zedek Medical Center ( Site 0186)

    Jerusalem, 9103102

    Study Coordinator, +97226555999

    Recruiting

  • Meir Medical Center ( Site 0181)

    Kfar Saba, 4428164

    Study Coordinator, +97297472555

    Recruiting

  • Sheba Medical Center ( Site 0180)

    Ramat Gan, 5265601

    Study Coordinator, +97235303030

    Recruiting

Other trials in Israel

China2 sites, 2 recruiting

  • Guangdong Provincial People s Hospital ( Site 0300)

    Guangzhou, Guangdong, 510120

    Study Coordinator, 02083525210

    Recruiting

  • Yunnan Province Cancer Hospital ( Site 0302)

    Kunming, Yunnan, 650107

    Study Coordinator, +8687168189037

    Recruiting

Other trials in China

Germany1 site, 1 recruiting

  • UniversitaetsklInikum Tuebingen ( Site 0192)

    Tübingen, Baden-Wurttemberg, 72076

    Study Coordinator, +4970712982795

    Recruiting

Other trials in Germany

Italy1 site, 1 recruiting

  • IRCCS - Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori" ( Site 0176)

    Meldola, Forli-Cesena, 47014

    Study Coordinator, 393487469100

    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

About this study

Official title: KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations

Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn:

  • About the safety of MK-1084 and if people tolerate it when taken with other treatments
  • How many people have the cancer respond (get smaller or go away) to the treatments
Read the detailed description

This is a substudy of the master protocol MK-3475-U01 (KEYMAKER-U01) - NCT04165798.

Per amendment 3, the MK-1084 + Cetuximab arm was discontinued.

Being tested
MK-1084, Patritumab deruxtecan, Sacituzumab tirumotecan, Cetuximab, Rescue Medications
Medical subject headings
Lung Neoplasms

What participants receive

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

  • MK-1084Drug

    Oral administration

  • Patritumab deruxtecanBiological

    Also called HER3-DXd, MK-1022, U3-1402

    IV infusion

  • Sacituzumab tirumotecanBiological

    Also called Sac-TMT, MK-2870, SKB264

    IV Infusion

  • CetuximabBiological

    Also called C225, Erbitux

    IV Infusion

  • Rescue MedicationsDrug

    Participants 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.

Study groups in NCT07286149
Study groupRoleWhat they receive
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.
Receives: Drug: MK-1084; Biological: Patritumab deruxtecan; Drug: Rescue Medications
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.
Receives: Drug: MK-1084; Biological: Sacituzumab tirumotecan; Drug: Rescue Medications
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.
Receives: Drug: MK-1084; Biological: Cetuximab

What is being measured

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

  1. Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

    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.

    Measured: Up to 42 days

  2. Number of Participants Who Experience an 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. The number of participants that experience AEs will be reported.

    Measured: Up to approximately 63 months

  3. Number of Participants Who Discontinue Study Treatment 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. The number of participants that discontinue study intervention due to an AE will be reported.

    Measured: Up to approximately 62 months

  4. Objective Response Rate (ORR)

    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.

    Measured: Up to approximately 63 months

Secondary outcomes (5)

  1. Duration of Response (DOR)

    For participants who demonstrate a confirmed CR (disappearance of all target lesions) or 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 63 months

  2. Progression-Free Survival (PFS)

    PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by 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 71 months

  3. Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC tau)

    Blood samples will be collected at multiple time points to estimate AUC tau.

    Measured: Predose and at designated time points post-dose (up to approximately 63 months)

  4. Maximum Plasma Concentration (Cmax)

    Blood samples will be collected at multiple time points to estimate Cmax.

    Measured: Predose and at designated time points post-dose (up to approximately 63 months)

  5. Minimum Observed Concentration (Ctrough)

    Blood samples will be collected at multiple time points to estimate Ctrough.

    Measured: Predose and at designated time points post-dose (up to approximately 63 months)

Timeline

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

  1. First posted16 Dec 2025
  2. Study start30 Apr 2026
  3. Primary completion17 Aug 2029 (estimated)
  4. Study completion13 Apr 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 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Participants will be enrolled and treated sequentially during dose escalation followed by parallel assignment in the expansion phase.
Masking
None (open label)
Enrolment
140 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07286149
Sponsor's protocol ID
3475-01F
Other IDs
MK-3475-01F, 2024-512248-47-00, U1111-1304-4707
Status last verified
Sep 2026
First submitted
17 Nov 2025
Last updated
1 Oct 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 1/2 study testing MK-1084, Patritumab deruxtecan and Sacituzumab tirumotecan in people with Lung Neoplasm Malignant, run by Merck Sharp & Dohme LLC at 29 sites in 11 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 6 inclusion and 15 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 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in United States, Brazil, Spain, Chile, Greece and 6 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Number of Participants Who Experience a Dose Limiting Toxicity (DLT) (time frame: Up to 42 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 NCT07286149.

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 1 Oct 2026.

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