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

Merck Sharp & Dohme (MSD)

Status and phase: Begins enrollment this month; Phase 2; Phase 1

Conditions: Lung Neoplasm Malignant

Treatments: Biological: Cetuximab; Drug: MK-1084; Drug: Rescue Medications; Biological: Patritumab deruxtecan; Biological: Sacituzumab tirumotecan

Study type: Interventional

Funder types: Industry

Identifiers

NCT07286149

2024-512248-47-00 (Registry Identifier)

3475-01F

U1111-1304-4707 (Registry Identifier)

MK-3475-01F (Other Identifier)

Details and patient eligibility

About

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

Full description

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

Enrollment: 190 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

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
• 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

Exclusion criteria

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
• 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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190 participants in 3 patient groups

MK-1084 + Patritumab deruxtecan (HER3-DXd)

Experimental group

Description:

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

Treatment:

Biological: Patritumab deruxtecan

Drug: MK-1084

MK-1084 + Sacituzumab tirumotecan (Sac-TMT)

Experimental group

Description:

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

Treatment:

Biological: Sacituzumab tirumotecan

Drug: Rescue Medications

Drug: MK-1084

MK-1084 + Cetuximab

Experimental group

Description:

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

Treatment:

Drug: MK-1084

Biological: Cetuximab