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Participants receive pembrolizumab 200 mg intravenous (IV) on Day 1 of every 21-day cycle (every 3 weeks, or Q3W) for up to 35 treatments.

Participants receive carboplatin target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m\^2 IV on Day 1 of every 21-day cycle (Q3W) for a maximum of 6 cycles OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m\^2 IV on Day 1 Q3W for a maximum of 6 cycles; participants with non-squamous histologies may go on to receive optional treatment with pemetrexed 500 mg/m\^2 IV on Day 1 Q3W.

pembrolizumab

carboplatin

paclitaxel

pemetrexed

Medical Director

In this study, participants with programmed cell death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) will be randomized to receive single agent pembrolizumab for up to 35 treatments or standard of care (SOC) platinum-based chemotherapy (carboplatin + paclitaxel or carboplatin + pemetrexed for 4 to 6 21-day cycles). Participants in the platinum-based chemotherapy arms with non-squamous tumor histologies may receive pemetrexed maintenance therapy after the 4 to 6 cycles of chemotherapy. The primary study hypothesis is that pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy.

Pembrolizumab-treated participants, who attain a confirmed complete response (CR) or who stop trial treatment after 35 administrations of study medication for reasons other than disease progression or intolerability, may consider stopping trial treatment. These participants may be eligible for re-treatment with pembrolizumab monotherapy after they have experienced radiographic disease according to protocol-defined criteria. Response or progression in the Second Course Phase will not count towards the objective response rate (ORR) and progression free survival (PFS) endpoints in this trial.

The global study for MK-3475-042 enrolled 1274 participants. Of the 1274 total participants enrolled in the global study, 92 were also enrolled in the China extension study for MK-3475-042 (NCT03850444).

Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)

A Randomized, Open Label, Phase III Study of Overall Survival Comparing Pembrolizumab (MK-3475) Versus Platinum Based Chemotherapy in Treatment Naïve Subjects With PD-L1 Positive Advanced or Metastatic Non-Small Cell Lung Cancer (Keynote 042)

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥50% is presented.

OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥20% is presented.

OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to death due to any cause. Participants without documented death at the time of the interim analysis were censored at the date of the last follow-up. The OS was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was OS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The OS for participants with a TPS ≥1% is presented.

PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥50% is presented.

PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥20% is presented.

PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was PFS in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The PFS for participants with a TPS ≥1% is presented.

ORR was determined for participants with a TPS of ≥50%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.

ORR was determined for participants with a TPS of ≥20%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.

ORR was determined for participants with a TPS of ≥1%. ORR was determined per RECIST 1.1 and was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1. The efficacy hypothesis was analyzed using a sequential testing strategy that involved testing a hypothesis only if the superiority of pembrolizumab over chemotherapy was established for all the preceding hypotheses. The order of testing was ORR in participants with TPS≥50%, then with TPS≥20%, and finally with TPS≥1%. The percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which does not necessarily have to have a causal relationship with this treatment. An AE could therefore be 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who experienced at least one AE is presented.

An AE was defined as any untoward medical occurrence in a participant administered a study treatment and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be 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 study treatment or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of study treatment, was also an AE. The number of participants who discontinued study treatment due to an AE is presented.

Merck Sharp & Dohme LLC

Population: All participants receiving ≥1 dose of study treatment. Per protocol, progression of cancer under study was not considered an AE unless related to study drug. Therefore, MedDRA preferred terms "Neoplasm progression", "Malignant neoplasm progression" \& "Disease progression" not related to study drug are excluded as AEs.

Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)

Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W.

Chemotherapy (SOC Treatment)

Eligible participants who stopped the initial course of pembrolizumab with Stable Disease (SD) or better but progressed after discontinuation may have been able to initiate a second course of pembrolizumab for up to 17 cycles (up to approximately 1 additional year) at the investigator's discretion.

Pembrolizumab Second Course

Participants received carboplatin at target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Participants were assessed for ECOG PS: Grade 0: Fully active, able to carry on all pre-disease performance without restriction; Grade 1: Restricted in physically strenuous activity but ambulatory \& able to carry out work of a light or sedentary nature; Grade 2: Ambulatory \& capable of all selfcare but unable to carry out any work activities, up \& about more than 50% of waking hours; Grade 3: Capable of only limited selfcare, confined to bed or chair more than 50% of waking hours; Grade 4: Completely disabled, cannot carry on any selfcare, totally confined to bed or chair or Grade 5: Dead.

Eastern Cooperative Oncology Group (ECOG) Performance Status (PS)

Participants were assessed for their PD-L1 tumor expression status by immunohistochemistry assay using tumor tissue from an archival or newly obtained biopsy. Participants with a tumor proportion score (TPS) were classified as follows: ≥50% = PD-L1 strongly positive; 1-49% = PD-L1 weakly positive; and \<1% = PD-L1 negative.

Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status

Participants were classified according to tumor histology: Squamous or Non-squamous. The tumor histology determined potential treatment regimen.

Tumor Histology

The Baseline Analysis Population consisted of all randomized participants who were alive at the time of randomization and had a Tumor Proportion Score (TPS) ≥1%.

Senior Vice President, Global Clinical Development

The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥50%.

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%

The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥20%.

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%

The analysis population included all participants who were alive at the time of randomization and had a TPS of ≥1%.

Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥50%

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥20%

Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) in Participants With a Tumor Proportion Score (TPS) of ≥1%

The analysis population consisted of all participants who received ≥1 dose of study treatment.

Number of Participants Who Experienced At Least One Adverse Event (AE)

Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)

Participants received pembrolizumab 200 mg by intravenous (IV) infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles). Some participants may have been eligible for re-treatment with pembrolizumab monotherapy after they had experienced radiographic disease as per protocol-defined criteria.

Participants received carboplatin at target dose Area Under Curve (AUC) 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + paclitaxel 200 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles) OR carboplatin target dose AUC 5 (maximum dose 750 mg) or AUC 6 (maximum dose 900 mg) + pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W for a maximum of 6 cycles (21-day cycles). Participants with non-squamous histologies received optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W

Spots Global Cancer Trial Database for Study of Pembrolizumab (MK-3475) Versus Platinum-Based Chemotherapy for Participants With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Advanced or Metastatic Non-Small Cell Lung Cancer (MK-3475-042/KEYNOTE-042)

Trial Identification

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Study Description

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