A Study of Calderasib (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)

Per Protocol Amendment 04, overall survival (OS) was moved to be a secondary outcome measure. Additionally, no new participants will be offered Second Course treatment for 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 calderasib by oral tablets until discontinuation criterion is met.

Drug: Calderasib · Biological: 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.

Other: Placebo · Biological: Pembrolizumab

Oral tablets

Oral tablets

IV infusion

Plazo: 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.

Plazo: Up to approximately 57 months

OS is defined as the time from randomization to death due to any cause.

Plazo: 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.

Plazo: 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.

Plazo: Up to approximately 80 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.

Plazo: Up to approximately 80 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

Plazo: 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.

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)