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

Phase 3

Recruiting

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: MK-1084; Other: Placebo; Biological: Pembrolizumab

• Registration Number: NCT06345729
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

This is a study evaluating the efficacy and safety of MK-1084 with pembrolizumab as first-line treatment in participants with locally advanced or metastatic non-small cell lung cancer (NSCLC) with identified Kirsten rat sarcoma viral oncogene homolog G12C (KRAS G12C) mutation and programmed cell death ligand 1 (PD-L1) tumor proportion score (TPS) ≥50%. There are two primary study hypotheses:

Hypothesis 1: Combination of MK-1084 and pembrolizumab is superior to placebo plus pembrolizumab with respect to progression free survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) by blinded independent central review (BICR).

Hypothesis 2: Combination of MK-1084 plus pembrolizumab is superior to placebo plus pembrolizumab with respect to overall survival (OS).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-03-28
• Study First Submitted QC: 2024-03-28
• Study First Posted: 2024-04-03
• Study Start: 2024-05-24
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-08
• Last Update Posted: 2025-09-10
• Primary Completion: 2029-02-19
• Study Completion: 2031-02-18

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MK-1084 with Pembrolizumab	MK-1084	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and MK-1084 by oral tablets once daily until discontinuation criterion is met.
Placebo with Pembrolizumab	Placebo	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.
MK-1084 with Pembrolizumab	Pembrolizumab	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and MK-1084 by oral tablets once daily until discontinuation criterion is met.
Placebo with Pembrolizumab	Pembrolizumab	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles and placebo by oral tablets once daily until discontinuation criterion is met.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS)	Up to approximately 42 months	PFS is defined as the time from randomization until either documented disease progression per Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) or death due to any cause, whichever occurs first. PFS as determined by blinded independent central review (BICR) will be presented.
Overall Survival (OS)	Up to approximately 56 months	OS is defined as the time from randomization to death due to any cause.

Secondary Outcome Measures

Name	Time	Method
Number of Participants Who Experience One or More Adverse Event (AEs)	Up to approximately 56 months	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who experience an AE will be presented.
Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score	Baseline and Up to approximately 24 months	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in dyspnea (EORTC QLQ-C30 Item 8) score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in dyspnea score, will be presented. A longer TTD indicates a better outcome.
Duration of Response (DOR)	Up to approximately 42 months	For participants who demonstrate confirmed CR or PR per RECIST 1.1 as assessed by BICR, duration of response is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Dyspnea (Item 8) Score	Baseline and Up to approximately 24 months	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant response to the question "Were you short of breath?" is scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C30 Item 8 will be presented. A higher score indicates a worse level of dyspnea.
Objective Response Rate (ORR)	Up to approximately 42 months	ORR is defined as the percentage of participants with Complete Response or Partial Response per RECIST1.1. The percentage of participants who experience CR or PR as assessed by BICR will be presented.
Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	Up to approximately 56 months	An AE is any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a preexisting condition that is temporally associated with the use of the Sponsor's product, is also an AE. The number of participants who discontinue study treatment due to an AE will be presented.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score	Baseline and Up to approximately 24 months	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C30 Items 1-5 will be presented. Higher scores indicate a better level of functioning.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score	Baseline and Up to approximately 24 months	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C30 Items 6-7 will be presented. Higher scores indicate a better level of functioning.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	Baseline and Up to approximately 24 months	The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in the score of EORTC QLQ-C30 Items 29 and 30 will be presented. Higher scores indicate a better overall health status.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score	Baseline and Up to approximately 24 months	The EORTC QLQ-C13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C13 Item 31 will be presented. A higher score indicates more frequent coughing.
Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Physical Functioning (Items 1-5) Score	Baseline and Up to approximately 24 months	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in physical functioning (EORTC QLQ-C30 Items 1-5) score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in physical functioning score, will be presented. A longer TTD indicates a better outcome.
Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Chest pain (Item 40) Score	Baseline and Up to approximately 24 months	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in chest pain (EORTC QLQ-C13 Item 40) score. The EORTC QLQ-C13 is lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline chest pain score, will be presented. A longer TTD indicates a better outcome.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-LC13) Chest pain (Item 40) Score	Baseline and Up to approximately 24 months	The EORTC QLQ-C13 is lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you had pain in your chest?" is scored on a 4-point scale (1=Not at All to 4=Very Much). The change from baseline in the score of EORTC QLQ-C13 Item 40 will be presented. A higher score indicates a worse level of chest pain.
Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	Baseline and Up to approximately 24 months	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in global health status (GHS) and quality of life (QoL) (EORTC QLQ-C30 Items 29 and 30) score. Participant responses to the questions "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" are scored on a 7-point scale (1= Very poor to 7=Excellent). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in GHS and QoL, will be presented. A longer TTD indicates a better outcome.
Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Role Functioning (Items 6 and 7) Score	Baseline and Up to approximately 24 months	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in role functioning (EORTC QLQ-C30 Items 6 and 7) score. The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in role functioning score, will be presented. A longer TTD indicates a better outcome.
Time to Deterioration (TTD) in European Organization for Research and Treatment of Cancer Quality of Life Lung Cancer-Specific Questionnaire Module (EORTC QLQ-C13) Cough (Item 31) Score	Baseline and Up to approximately 24 months	TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in cough (EORTC QLQ-C13 Item 31) score. The EORTC QLQ-C13 is lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant response to the question "Have you coughed?" is scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in cough score, will be presented. A longer TTD indicates a better outcome.

Trial Locations

Locations (190)

CBCC Global Research, Inc. ( Site 0123); 🇺🇸 Bakersfield, California, United States

Beverly Hills Cancer Center ( Site 0116); 🇺🇸 Beverly Hills, California, United States

Mount Sinai Cancer Center ( Site 0137); 🇺🇸 Miami Beach, Florida, United States

Orchard Healthcare Research Inc. ( Site 0115); 🇺🇸 Skokie, Illinois, United States

Truman Medical Center ( Site 0126); 🇺🇸 Kansas City, Missouri, United States

Cox Medical Center North ( Site 0133); 🇺🇸 Springfield, Missouri, United States

St. Vincent Frontier Cancer Center-Research ( Site 0105); 🇺🇸 Billings, Montana, United States

Atlantic Health System Morristown Medical Center ( Site 0121); 🇺🇸 Morristown, New Jersey, United States

New York Oncology Hematology, P.C. ( Site 0132); 🇺🇸 Albany, New York, United States

University of Cincinnati Medical Center-University of Cincinnati Cancer Center ( Site 0103); 🇺🇸 Cincinnati, Ohio, United States

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