Pembrolizumab plus MK-1084 for NSCLC with KRAS G12C mutation

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This Phase 2 interventional trial enrolls people with advanced or metastatic nonsquamous non‑small cell lung cancer whose tumors or ctDNA harbor the KRAS G12C mutation. Participants receive the KRAS G12C targeted agent MK-1084 in combination with the PD‑1 inhibitor pembrolizumab, with protocol-defined use of other agents as specified by treatment arms. The study's main goals are to characterize safety and to measure how often tumors shrink or disappear on treatment. Participants must provide tumor tissue or ctDNA for mutation confirmation and will be monitored with regular safety assessments and imaging to track response.

Why it matters

Who can join: the full rules

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 history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or severe corneal disease that prevents/delays corneal healing
* 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 (ILD) that required steroids, has current pneumonitis/ILD, or has suspected ILD or pneumonitis that cannot be ruled out by standard diagnostic assessments at screening
* Has a history of stem cell/solid organ transplant
* Has not adequately recovered from major surgery or has ongoing surgical complications

Where it's running

• Clermont Oncology Center ( Site 0041)
  Clermont, Florida, United States Recruiting
• Sanford Health Roger Maris Cancer Center ( Site 0039)
  Fargo, North Dakota, United States Recruiting
• Sanford Cancer Center Oncology Clinic ( Site 0038)
  Sioux Falls, South Dakota, United States Recruiting
• Fundacion Arturo Lopez Perez ( Site 0167)
  Santiago, Region M. de Santiago, Chile Recruiting
• Centro de Oncología de Precisión ( Site 0160)
  Santiago, Region M. de Santiago, Chile Recruiting
• Bradfordhill ( Site 0168)
  Santiago, Region M. de Santiago, Chile Recruiting

Study contacts

• Study coordinator: Toll Free Number
• Email: Trialsites@msd.com
• Phone: 1-888-577-8839

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.