This is a Phase 3, randomized, active-controlled, parallel-group, double-blind, multisite study of MK-1084 in combination with pembrolizumab versus pembrolizumab and placebo. Participants with newly diagnosed metastatic Stage IV NSCLC with PD-L1 TPS ≥50% and KRAS G12C mutation, and with no prior treatment for Stage IV disease will be enrolled in the study.

• Approximately 600 participants with measurable disease by RECIST 1.1 will be randomly assigned in a 1:1 ratio to Arm A or Arm B:
  • MK-1084 100 mg qd po combined with pembrolizumab 200 mg q3w IV (Arm A)
  • Placebo qd po combined with pembrolizumab 200 mg q3w IV (Arm B
• Randomization will be stratified by ECOG, presence of brain metastases and prior exposure to immunotherapy in neoadjuvant/adjuvant setting

• The primary endpoint of this study is PFS by BICR according to RECIST 1.1
• The key secondary efficacy endpoint is OS

1. Has a histologically or cytologically confirmed diagnosis of NSCLC. Note: Mixed tumors will be characterized by the predominant cell type; if small cell elements are present, the participant is ineligible.
2. Has newly diagnosed Stage IV (M1a, M1b, or M1c) by AJCC Staging Manual, Version 8
3. Has measurable (eligible for selection as target lesions) disease based on RECIST 1.1, as determined by the local site investigator/radiology assessment. Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable if they have shown documented growth since the completion of radiation
4. Has provided tumor tissue that demonstrates PD-L1 expression in ≥50% of tumor cells (TPS ≥50%) as assessed by IHC 22C3 at a central laboratory. Note: Assessment of PD-L1 expression must be made before randomization.
5. Has provided tumor tissue that demonstrates presence of KRAS G12C mutation as assessed at a central laboratory. Note: Assessment of presence of KRAS G12C mutation must be made before randomization.
6. Has life expectancy of at least 3 months.
7. Has ECOG performance status of 0 or 1 assessed within 7 days before randomization.
8. Has adequate organ function. All screening laboratory tests should be performed within 10 days before the first dose of study intervention.
9. Is an individual of any sex/gender, at least 18 years of age, at the time of providing the informed consent.
10. Archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion not previously irradiated has been provided.
11. Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with hormone replacement or participants who have ≤Grade 2 neuropathy are eligible.

1. Has Diagnosis of small cell lung cancer. For mixed tumors, if small cell elements are present, the participant is ineligible.
2. Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea).
3. Has a known history of, or active, neurologic paraneoplastic syndrome
4. Has an active infection requiring systemic therapy.
5. 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 QTcF interval to >470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention
6. 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
7. Has one or more of the following ophthalmological findings/conditions: intraocular pressure >21 mm Hg and/or any diagnosis of glaucoma (eg, open-angle, closed-angle, or mixed), diagnosis of central serous retinopathy, retinal vein occlusion, or retinal artery occlusion, diagnosis of retinal degenerative disease (eg, wet or dry macular degeneration)
8. Is unable to swallow orally administered medication, or has a gastrointestinal disorder affecting absorption (eg, gastrectomy, partial bowel obstruction, or malabsorption).
9. Received prior systemic anticancer therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC
10. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). Note: Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent in the neoadjuvant or adjuvant setting for nonmetastatic resectable NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of metastatic NSCLC.
11. Has received previous treatment with an agent targeting KRAS mutations.
12. Received medications, foods, or herbal supplements considered strong inhibitors of CYP3A, strong inducers of CYP3A, substrates of CYP3A with a narrow therapeutic index, P-gp substrates or sensitive substrates of OATP1B within 2 weeks of study start
13. Received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention
14. Has received radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
15. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Refer to Section 6.5 for information on COVID-19 vaccines.
16. Is expected to require any other form of antineoplastic therapy for NSCLC, including radiation therapy, while on study. Exception: radiation to the brain may be allowed during the study after Sponsor consultation. Prophylactic cranial irradiation is not permitted during the study.
17. Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
18. Has known active CNS metastases and/or carcinomatous meningitis. Participants with brain metastases may participate provided they are:

• clinically stable for at least 2 weeks, and

• have no evidence of new or enlarging brain metastases, and

• are off steroids 3 days prior to dosing with study medication.

  Stable brain metastases by this definition should be established prior to the first dose of study medication. Participants with known untreated,
  asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion >1.5
  cm) may participate, but will require regular imaging of the brain as a site of disease number.

19. 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.
20. Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
21. Active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.
22. History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. Note: Lymphangitic spread of the NSCLC is not exclusionary.