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)-China Extension Study
- Conditions
- Non-small Cell Lung Cancer
- Interventions
- Registration Number
- NCT03850444
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
In the China extension study, Chinese 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). Chinese 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 extension study hypothesis is that pembrolizumab prolongs overall survival (OS) compared to SOC chemotherapy in Chinese participants.
- Detailed Description
The China extension study enrolled 262 participants. Of the 262 total participants enrolled, 92 were also previously enrolled in the global study for MK-3475-042 (NCT02220894).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 262
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pembrolizumab pembrolizumab Participants receive pembrolizumab 200 mg by IV infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles). Participants who stop the initial course of pembrolizumab due to complete response or complete the initial course of pembrolizumab and have stable disease, but progress after discontinuation, are eligible for a second course of pembrolizumab for up to an additional 1 year (17 additional 21-day cycles). SOC Treatment carboplatin Participants receive carboplatin at target dose Area Under the 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 receive optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W. SOC Treatment paclitaxel Participants receive carboplatin at target dose Area Under the 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 receive optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W. SOC Treatment pemetrexed Participants receive carboplatin at target dose Area Under the 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 receive optional additional maintenance treatment with pemetrexed 500 mg/m\^2 by IV infusion on Day 1 Q3W.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% Up to 23.2 months OS was determined for participants with a TPS of ≥20% and was defined as the time from randomization until death due to any cause. Participants without documented death at the time of the 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 OS for participants with a TPS ≥20% is presented.
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% Up to 23.2 months OS was determined for participants with a TPS of ≥50% and was defined as the time from randomization until death due to any cause. Participants without documented death at the time of the 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 OS for participants with a TPS ≥50% is presented.
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% Up to 23.2 months OS was determined for participants with a TPS of ≥1% and was defined as the time from randomization until death due to any cause. Participants without documented death at the time of the 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 OS for participants with a TPS ≥1% is presented.
- Secondary Outcome Measures
Name Time Method 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% Up to 23.2 months PFS was determined for participants with a TPS of ≥50% and was defined as the time from randomization until 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 or progression in non-target lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants with a TPS ≥50% is presented.
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% Up to 23.2 months PFS was determined for participants with a TPS of ≥20% and was defined as the time from randomization until 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 or progression in non-target lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants with a TPS ≥20% is presented.
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% Up to 23.2 months PFS was determined for participants with a TPS of ≥1% and was defined as the time from randomization until 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 or progression in non-target lesions was also considered PD. The PFS per RECIST 1.1 was calculated using the product-limit (Kaplan-Meier) method for censored data. The PFS for participants with a TPS ≥1% is presented.
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% Up to 23.2 months 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 and non-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 percentage of participants who had a TPS ≥50% and who experienced a CR or PR is presented.
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% Up to 23.2 months 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 and non-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 percentage of participants who had a TPS ≥20% and who experienced a CR or PR is presented.
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% Up to 23.2 months 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 and non-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 percentage of participants who had a TPS ≥1% and who experienced a CR or PR is presented.
Number of Participants Who Experienced At Least One Adverse Event (AE) Up to 59.7 months 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.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) Up to 56.7 months 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 discontinued study treatment due to an AE is presented.