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

NCT07286149 | Recruiting Phase 1 FDA Drug

• 4 other identifiers: 3475-01FMK-3475-01F2024-512248-47-00U1111-1304-4707
• Study Type: interventional
• Target: 190
• Locations: 10 countries
• Sites: 21

Brief 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. 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

Conditions

Lung Neoplasm Malignant

Outcome Measures

Primary Outcomes (4)

• 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.

  Up to 42 days

• 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.

  Up to approximately 65 months

• 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.

  Up to approximately 64 months

• 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.

  Up to approximately 65 months

Secondary Outcomes (5)

• Duration of Response (DOR)

  Up to approximately 65 months

• Progression-Free Survival (PFS)

  Up to approximately 124 months

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

  Predose and at designated time points post-dose (up to approximately 65 months)

• Maximum Plasma Concentration (Cmax)

  Predose and at designated time points post-dose (up to approximately 65 months)

• Minimum Observed Concentration (Ctrough)

  Predose and at designated time points post-dose (up to approximately 65 months)

Study Arms (3)

MK-1084 + Patritumab deruxtecan (HER3-DXd)

EXPERIMENTAL

Participants will receive MK-1084 and HER3-DXd until discontinuation due to toxicity, adverse event (AE) or at the discretion of an investigator.

Drug: MK-1084; Biological: Patritumab deruxtecan

MK-1084 + Sacituzumab tirumotecan (Sac-TMT)

EXPERIMENTAL

Participants will receive MK-1084 and sac-TMT until discontinuation due to toxicity, AE or at the discretion of an investigator.

Drug: MK-1084; Biological: Sacituzumab tirumotecan; Drug: Rescue Medications

MK-1084 + Cetuximab

EXPERIMENTAL

Participants will receive MK-1084 and cetuximab until discontinuation due to toxicity, AE or at the discretion of an investigator.

Drug: MK-1084; Biological: Cetuximab

Interventions

Rescue Medications DRUG

Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are histamine -1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent) for prevention of chemotherapy induced nausea and vomiting.

MK-1084 + Sacituzumab tirumotecan (Sac-TMT)

MK-1084 DRUG

Oral administration

MK-1084 + Cetuximab; MK-1084 + Patritumab deruxtecan (HER3-DXd); MK-1084 + Sacituzumab tirumotecan (Sac-TMT)

Cetuximab BIOLOGICAL

IV Infusion

Also known as: C225, Erbitux

MK-1084 + Cetuximab

Patritumab deruxtecan BIOLOGICAL

IV infusion

Also known as: HER3-DXd, MK-1022, U3-1402

MK-1084 + Patritumab deruxtecan (HER3-DXd)

Sacituzumab tirumotecan BIOLOGICAL

IV Infusion

Also known as: Sac-TMT, MK-2870, SKB264

MK-1084 + Sacituzumab tirumotecan (Sac-TMT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Provides archival tumor tissue sample of a tumor lesion not previously irradiated
• Has provided tissue prior to treatment allocation/randomization from a newly obtained 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

You may not qualify if:

• 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
• 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 previous treatment with an agent targeting KRAS
• 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 history of (noninfectious) pneumonitis/ interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD
• Has an active infection requiring systemic therapy
• Have not adequately recovered from major surgery or have ongoing surgical complications

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Daiichi Sankyo: collaborator

Study Sites (21)

Clermont Oncology Center ( Site 0041)

Clermont, Florida, 34711, United States

RECRUITING

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

Chicago, Illinois, 60612, United States

RECRUITING

Providence Portland Medical Center ( Site 0043)

Portland, Oregon, 97213, United States

RECRUITING

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

Portland, Oregon, 97225, United States

RECRUITING

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

Barretos, São Paulo, 14784-400, Brazil

RECRUITING

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

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

RECRUITING

Hospital Paulistano ( Site 0280)

São Paulo, São Paulo, 01321001, Brazil

RECRUITING

Centro de Estudios Clínicos SAGA-CECSAGA ( Site 0162)

Santiago, Region M. de Santiago, 7500653, Chile

RECRUITING

FALP ( Site 0161)

Santiago, Region M. de Santiago, 7500921, Chile

RECRUITING

Bradfordhill ( Site 0160)

Santiago, Region M. de Santiago, 8420383, Chile

RECRUITING

Guangdong Provincial People s Hospital ( Site 0300)

Guangzhou, Guangdong, 510120, China

RECRUITING

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

Athens, Attica, 115 27, Greece

RECRUITING

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

Athens, Attica, 115 28, Greece

RECRUITING

Queen Mary Hospital ( Site 0230)

Hong Kong, 000000, Hong Kong

RECRUITING

Shaare Zedek Medical Center ( Site 0186)

Jerusalem, 9103102, Israel

RECRUITING

Sheba Medical Center ( Site 0180)

Ramat Gan, 5265601, Israel

RECRUITING

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

Meldola, Forli-Cesena, 47014, Italy

RECRUITING

Severance Hospital, Yonsei University Health System ( Site 0080)

Seoul, 03722, South Korea

RECRUITING

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

Hospitalet, Barcelona, 08908, Spain

RECRUITING

Hospital Clinic de Barcelona ( Site 0092)

Barcelona, 08036, Spain

RECRUITING

Hospital Universitario Virgen Macarena ( Site 0093)

Seville, 41009, Spain

RECRUITING

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Lung Neoplasms

Interventions

patritumab deruxtecan; Cetuximab

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Central Study Contacts

Toll Free Toll Free Number

CONTACT

1-888-577-8839; Trialsites@msd.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants will be enrolled and treated sequentially during dose escalation followed by parallel assignment in the expansion phase.

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 16, 2025
• Study Start: April 30, 2026
• Primary Completion (Estimated): August 11, 2031
• Study Completion (Estimated): April 13, 2032
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share

Locations

US (4); KR (1); IL (2); BR (3); CN (1); CL (3); ES (3); GR (2); HK (1); IT (1)