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)

Merck Sharp & Dohme (MSD)

Status and phase: Enrolling; Phase 2

Conditions: Malignant Neoplasm

Treatments: Drug: Carboplatin; Drug: MK-1084; Biological: Cetuximab; Biological: Pembrolizumab; Drug: Pemetrexed

Study type: Interventional

Funder types: Industry

Identifiers

NCT07252739

3475-01J

U1111-1321-3999 (Registry Identifier)

2025-521939-36-00 (Registry Identifier)

Details and patient eligibility

About

Researchers want to learn if using a study medicine called MK-1084 can help treat 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.

Enrollment: 130 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 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

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 HIV-infection with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• 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
• 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 that required steroids or has current pneumonitis/interstitial lung disease
• Has a history of stem cell/solid organ transplant
• Has not adequately recovered from major surgery or has ongoing surgical complications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

130 participants in 3 patient groups

Arm 1

Experimental group

Description:

Participants receive 400 mg of Pembrolizumab every 6 weeks, Carbo platin every 3 weeks and 500 mg/m\^2 of Pemetrexed every 3 weeks.

Treatment:

Drug: Pemetrexed

Biological: Pembrolizumab

Drug: Carboplatin

Arm 2

Experimental group

Description:

Participants receive 400 mg of Pembrolizumab every 6 weeks, and MK-1084 dose regimen

Treatment:

Biological: Pembrolizumab

Drug: MK-1084

Arm 3

Experimental group

Description:

Participants receive 400 mg of Pembrolizumab every 6 weeks, 500 mg/m\^2 Cetuximab every 2 weeks, and MK-1084 dose regimen

Treatment:

Biological: Cetuximab

Biological: Pembrolizumab

Drug: MK-1084