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Combining MK-1084 and Pembrolizumab for Advanced Lung Cancer with Specific Genetic Mutations

A Phase 3, Randomized, Double-blind, Multicenter Study of MK-1084 in Combination With Pembrolizumab Compared With Pembrolizumab Plus Placebo as Firstline Treatment of Participants With KRAS G12C-Mutant, Locally Advanced or Metastatic NSCLC With PD-L1 TPS ≥50% (KANDLELIT-004)

Phase 3 Interventional Merck Sharp & Dohme LLC · NCT06345729

This study is testing if a new combination of two drugs, MK-1084 and pembrolizumab, can help people with advanced lung cancer who have specific genetic mutations live longer and feel better.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorMerck Sharp & Dohme LLC Industry-sponsored
Drugs / interventionschemotherapy, radiation, pembrolizumab
Locations219 sites (Bakersfield, California and 218 other locations)
Trial IDNCT06345729 on ClinicalTrials.gov

What this trial studies

This study evaluates the effectiveness and safety of MK-1084 in combination with pembrolizumab as a first-line treatment for patients with metastatic non-small cell lung cancer (NSCLC) who have the KRAS G12C mutation and a PD-L1 tumor proportion score of 50% or higher. The trial tests two main hypotheses: that the combination treatment improves progression-free survival and overall survival compared to a placebo plus pembrolizumab. Participants will be monitored for their response to treatment using established criteria for solid tumors.

Who should consider this trial

Good fit: Ideal candidates include individuals with newly diagnosed Stage IV NSCLC who have the KRAS G12C mutation and PD-L1 expression in at least 50% of their tumor cells.

Not a fit: Patients without the KRAS G12C mutation or those with lower PD-L1 expression may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve survival outcomes for patients with a specific type of advanced lung cancer.

How similar studies have performed: Other studies have shown promising results with similar immunotherapy approaches, indicating potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
The main inclusion and exclusion criteria include but are not limited to the following:

Inclusion Criteria:

* Has histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
* Has newly diagnosed Stage IIIB/IIIC NSCLC, not eligible for curative resection or curative chemotherapy/radiation as determined by a multidisciplinary tumor board and/or by radiation oncologist, surgeon, and medical oncologist or Stage IV (M1a, M1b, or M1c) by American Joint Committee on Cancer (AJCC) Staging Manual, Version 8
* Provides an archival tumor tissue sample (≤5 years) or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of kirsten rat sarcoma (KRAS) G12C mutation status, PD-L1 status, and biomarker research
* If have had adverse events (AEs) due to previous anticancer therapies, must have recovered to \< Grade 1 or baseline
* If human immunodeficiency virus (HIV)-infected, must have well controlled HIV on antiretroviral therapy (ART)
* If Hepatitis B surface antigen (HBsAg) positive, have received Hepatitis B Virus (HBV) antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
* If a participant has a history of Hepatitis C virus (HCV) infection, HCV viral load is undetectable

Exclusion Criteria:

* Has diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible
* Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease
* Has known history of, or active, neurologic paraneoplastic syndrome
* Has an active infection requiring systemic therapy, with exceptions
* Has uncontrolled, significant cardiovascular disease or cerebrovascular disease
* Has one or more of the following ophthalmological findings/conditions: intraocular pressure \>21 mmHg and/or any diagnosis of glaucoma, diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease
* Has received prior systemic anticancer therapy for their locally advanced or metastatic NSCLC
* Has received radiation therapy to the lung that is \>30 Gray within 6 months of start of study intervention
* Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not required corticosteroids, and not have had radiation pneumonitis
* Has known active central nervous system metastases and/or carcinomatous meningitis
* Known additional malignancy that is progressing or has required active treatment within the past 3 years
* Has active autoimmune disease that has required systemic treatment in the past 2 years
* Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
* Is HIV-infected and has a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
* Has history of allogenic tissue/solid organ transplant
* Has not fully recovered from any effects of major surgical procedure

Where this trial is running

Bakersfield, California and 218 other locations

+169 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Non-small Cell Lung CancerProgrammed Cell Death-1Programmed Cell Death 1 Ligand 1Programmed Cell Death 1 Ligand 2Kirsten rat sarcoma viral oncogene homolog G12C
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.