A Study of MK-1084 Plus Pembrolizumab (MK-3475) in Participants With KRAS G12C Mutant, Metastatic Non-small Cell Lung Cancer (NSCLC) With Programmed Cell Death Ligand 1 (PD-L1) Tumor Proportion Score (TPS) ≥50% (MK-1084-004)

Launched by MERCK SHARP & DOHME LLC · Mar 28, 2024

Keywords

ClinConnect Summary

This clinical trial is investigating a new combination treatment for patients with a specific type of advanced lung cancer known as non-small cell lung cancer (NSCLC). Participants in this study will receive a medication called MK-1084 along with pembrolizumab, which is an existing cancer treatment. The goal is to see if this combination works better than a placebo (a treatment with no active ingredients) combined with pembrolizumab, particularly in helping to prolong the time patients live without their cancer getting worse and improving overall survival.

To be eligible for this trial, patients need to have a confirmed diagnosis of metastatic NSCLC with a specific genetic mutation called KRAS G12C and a high level of a protein called PD-L1 in their tumor cells. Other requirements include being at least 18 years old and having a life expectancy of at least three months. Participants can expect regular check-ups and monitoring during the trial, and they will be asked to follow certain health guidelines. It’s important to note that individuals with certain health conditions or who have received specific previous treatments may not be eligible to join.

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Eligibility criteria

• The main inclusion and exclusion criteria include but are not limited to the following:
• Inclusion Criteria:
• • Has a histologically or cytologically confirmed diagnosis of NSCLC
• • Has newly diagnosed Stage IV NSCLC by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
• • Has measurable disease based on RECIST 1.1
• • Has provided tumor tissue that demonstrates PD-L1 expression in ≥50% of tumor cells
• • Has provided tumor tissue that demonstrates presence of KRAS G12C mutation
• • Has life expectancy of at least 3 months
• • Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 assessed within 7 days before randomization
• • For participant assigned male sex at birth: If capable of producing sperm, participant must agree to the following during the study treatment period and for at least 10 days after the last dose of oral intervention: Either be abstinent or must agree to use male condom plus additional contraceptive method.
• • For participant assigned female sex at birth: Either be a person of nonchildbearing potential (PONCBP) or must agree to follow contraceptive guidance during the study treatment period and for at least 10 days after the last dose of oral intervention and 120 days after the last dose of pembrolizumab. Must abstain from breastfeeding during the study intervention period and for at least 120 days after study intervention.
• • Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy (ART).
• • Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load before randomization
• Exclusion Criteria:
• • Diagnosis of small cell lung cancer
• • Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
• • Has a known history of, or active, neurologic paraneoplastic syndrome
• • Has an active infection requiring systemic therapy
• • Has uncontrolled, 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 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
• • Is considered a poor medical risk due to a serious, uncontrolled medical disorder or nonmalignant systemic disease. Examples include, but are not limited to, uncontrolled major seizure disorder, unstable spinal cord compression, or superior vena cava syndrome.
• • Has one or more of the following ophthalmological findings/conditions: intraocular diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease pressure \>21 mm Hg and/or any diagnosis of glaucoma
• • Is unable to swallow orally administered medication, or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, or malabsorption)
• • Received prior systemic anticancer therapy for their metastatic NSCLC
• • Received prior therapy with an anti-programmed cell death-1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor within 12 months before diagnosis of metastatic NSCLC
• • Has received radiotherapy within 2 weeks of start of study intervention
• • Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration
• • Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• • 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
• • Active autoimmune disease that has required systemic treatment in the past 2 years
• • History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
• • HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
• • History of allogeneic tissue/solid organ transplant
• • Has not fully recovered from any effects of major surgical procedure. Surgical procedures that required general anesthesia must be completed at least 2 weeks before first study intervention administration.