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

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03850444
• Collaborator: (none)
• Enrollment: 262
• Arms: 2
• Anticipated Duration (Months): 73.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-small Cell Lung Cancer	Biological: pembrolizumab; Drug: carboplatin; Drug: paclitaxel; Drug: pemetrexed	Phase 3

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).

Study Design

• Study Type: Interventional
• Actual Enrollment: 262 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: Aug 1, 2016
• Actual Primary Completion Date: Sep 4, 2018
• Anticipated Study Completion Date: Sep 12, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pembrolizumab 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.	Biological: pembrolizumab; Other Names: MK-3475 KEYTRUDA®
Active Comparator: SOC Treatment 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.	Drug: carboplatin; Other Names: PARAPLATIN® ; Drug: paclitaxel; Other Names: TAXOL® ; Drug: pemetrexed; Other Names: ALIMTA®

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)]

   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 OS for participants with a TPS ≥50% is presented.

2. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)]

   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 OS for participants with a TPS ≥20% is presented.

3. Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)]

   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 OS for participants with a TPS ≥1% is presented.

Secondary Outcome Measures

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% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)]

   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 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.

2. 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% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)]

   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 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.

3. 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% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)]

   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 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.

4. 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% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 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.

5. 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% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 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.

6. 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% [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 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.

7. Number of Participants Who Experienced At Least One Adverse Event (AE) [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 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 can 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. These safety results are based on a 04-September-2018 data cutoff date.

8. Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE) [Through Database Cutoff Date of 04-September-2018 (up to approximately 23 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 can 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. These safety results are based on a 04-September-2018 data cutoff date.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria:

• Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC

• PD-L1 positive tumor

• Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

• Life expectancy of at least 3 months

• No prior systemic chemotherapy for the treatment of the participant's advanced or metastatic disease (treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as completed at least 6 months prior to diagnosis of advanced or metastatic disease)

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1

• Adequate organ function

• No prior malignancy, with the exception of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, or in situ cancer, or has undergone potentially curative therapy with no evidence of that disease recurrence for 5 years since initiation of that therapy

• Submission of formalin-fixed diagnostic tumor tissue (in the case of participants having received adjuvant systemic therapy, the tissue should be taken after completion of this therapy)

• Female participants of childbearing potential must have a negative urine or serum pregnancy test and must be willing to use two adequate barrier methods of contraception or a barrier method plus a hormonal method starting with the screening visit through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study

• Male participants with a female partner(s) of childbearing potential must be willing to use two adequate barrier methods of contraception from screening through 120 days after the last dose of pembrolizumab or 180 days after the last dose of chemotherapeutic agents used in the study

Exclusion criteria:

• Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or is echinoderm microtubule-associated protein-like 4 (EML4) gene/anaplastic lymphoma kinase (ALK) gene fusion positive

• Currently participating or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of study therapy

• No tumor specimen evaluable for PD-L1 expression by the central study laboratory

• Squamous histology and received carboplatin in combination with paclitaxel in the adjuvant setting

• Is receiving systemic steroid therapy ≤3 days prior to the first dose of study therapy or receiving any other form of immunosuppressive medication with the exception of daily steroid replacement therapy

• The NSCLC can be treated with curative intent with either surgical resection and/or chemoradiation

• Expected to require any other form of systemic or localized antineoplastic therapy while on study

• Any prior systemic cytotoxic chemotherapy, biological therapy or major surgery within 3 weeks of the first dose of study therapy; received lung radiation therapy >30 Gy within 6 months of the first dose of study therapy

• Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)

• Known central nervous system metastases and/or carcinomatous meningitis

• Active autoimmune disease that has required systemic treatment in the past 2 years

• Had allogeneic tissue/solid organ transplantation

• Interstitial lung disease or history of pneumonitis that has required oral or IV steroids

• Has received or will receive a live vaccine within 30 days prior to the first study therapy (seasonal flu vaccines that do not contain live vaccine are permitted)

• Active infection requiring intravenous systemic therapy

• Known history of human immunodeficiency virus (HIV)

• Known active Hepatitis B or C

• Regular user (including "recreational use") of any illicit drugs or had a recent history (within the last year) of substance abuse (including alcohol)

• Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 9, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT03850444
• Other Study ID Numbers: 3475-042 China Extension; 152877; MK-3475-042; KEYNOTE-042
• First Posted: Feb 21, 2019
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Merck Sharp & Dohme LLC: Programmed Cell Death-1 (PD-1); Programmed Cell Death 1; PD1; Programmed Cell Death Ligand 1 (PD-L1); PDL1
• Additional relevant MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Paclitaxel; Carboplatin; Pembrolizumab; Pemetrexed

Study Results

Participant Flow

Recruitment Details	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).
Pre-assignment Detail	These interim results are based on a database cutoff date of 04-September-2018, at which time 137 participants were ongoing in the study.

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	Participants received pembrolizumab 200 mg by IV infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles)	Participants received 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Period Title: Overall Study
STARTED	128	134
COMPLETED	0	0
NOT COMPLETED	128	134

Baseline Characteristics

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension	Total
Arm/Group Description	Participants received pembrolizumab 200 mg by IV infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles)	Participants received 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W	Total of all reporting groups
Overall Participants	128	134	262
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.9 (8.1)	61.5 (8.0)	61.2 (8.1)
Sex: Female, Male (Count of Participants)
Female	23 18%	15 11.2%	38 14.5%
Male	105 82%	119 88.8%	224 85.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	128 100%	134 100%	262 100%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	0 0%	0 0%	0 0%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (Count of Participants)
ECOG PS=0	31 24.2%	29 21.6%	60 22.9%
ECOG PS=1	97 75.8%	105 78.4%	202 77.1%
Programmed Cell Death-Ligand 1 (PD-L1) Tumor Status (Count of Participants)
TPS=≥50%	72 56.3%	74 55.2%	146 55.7%
TPS=20-49%	29 22.7%	29 21.6%	58 22.1%
TPS=1-19%	27 21.1%	31 23.1%	58 22.1%
TPS=<1%	0 0%	0 0%	0 0%
Tumor Histology (Count of Participants)
Squamous	71 55.5%	76 56.7%	147 56.1%
Non-squamous	57 44.5%	58 43.3%	115 43.9%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%
Description	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 OS for participants with a TPS ≥50% is presented.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	72	74
Median (95% Confidence Interval) [Months]	20.0	14.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.38 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio based on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), and histology (squamous vs. non-squamous).

2. Primary Outcome

Title	Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%
Description	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 OS for participants with a TPS ≥20% is presented.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	101	103
Median (95% Confidence Interval) [Months]	20.0	13.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio based on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%), and histology (squamous vs. non-squamous).

3. Primary Outcome

Title	Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%
Description	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 OS for participants with a TPS ≥1% is presented.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	128	134
Median (95% Confidence Interval) [Months]	20.0	13.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.65
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio based on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%), and histology (squamous vs. non-squamous).

4. Secondary Outcome

Title	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%
Description	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 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.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	72	74
Median (95% Confidence Interval) [Months]	8.3	6.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.57 to 1.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio based on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), and histology (squamous vs. non-squamous).

5. Secondary Outcome

Title	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%
Description	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 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.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	101	103
Median (95% Confidence Interval) [Months]	6.3	6.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.99
	Confidence Interval	(2-Sided) 95%; 0.70 to 1.39
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio based on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%), and histology (squamous vs. non-squamous).

6. Secondary Outcome

Title	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%
Description	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 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.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	128	134
Median (95% Confidence Interval) [Months]	6.3	6.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.74 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments	Hazard ratio based on Cox regression model with treatment as a covariate stratified by ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%), and histology (squamous vs. non-squamous).

7. Secondary Outcome

Title	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%
Description	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.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	72	74
Number (95% Confidence Interval) [Percentage of participants]	41.7 32.6%	24.3 18.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	r Difference in Percentage (DP)
	Estimated Value	17.2
	Confidence Interval	(2-Sided) 95%; 1.8 to 31.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	DP for pembrolizumab vs. chemotherapy based on Miettinen & Nurminen method stratified by ECOG PS (0 vs. 1) and histology (squamous vs. non-squamous).

8. Secondary Outcome

Title	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%
Description	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.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	101	103
Number (95% Confidence Interval) [Percentage of participants]	35.6 27.8%	24.3 18.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage (DP)
	Estimated Value	11.3
	Confidence Interval	(2-Sided) 95%; -1.4 to 23.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	DP for pembrolizumab vs. chemotherapy based on Miettinen & Nurminen method stratified by ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%), and histology (squamous vs. non-squamous).

9. Secondary Outcome

Title	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%
Description	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.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	128	134
Number (95% Confidence Interval) [Percentage of participants]	32.8 25.6%	24.6 18.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab-China Extension, Chemotherapy (SOC Treatment)-China Extension
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage (DP)
	Estimated Value	8.0
	Confidence Interval	(2-Sided) 95%; -3.0 to 18.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	DP for pembrolizumab vs. chemotherapy based on Miettinen & Nurminen method stratified by ECOG PS (0 vs. 1), PD-L1 expression status (TPS=≥50% vs. TPS=1-49%), and histology (squamous vs. non-squamous).

10. Secondary Outcome

Title	Number of Participants Who Experienced At Least One Adverse Event (AE)
Description	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 can 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. These safety results are based on a 04-September-2018 data cutoff date.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	128	125
Count of Participants [Participants]	125 97.7%	124 92.5%

11. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)
Description	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 can 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. These safety results are based on a 04-September-2018 data cutoff date.
Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pembrolizumab-China Extension	Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	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 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
Measure Participants	128	125
Count of Participants [Participants]	21 16.4%	23 17.2%

Adverse Events

Time Frame	Through Database Cutoff Date of 04-September-2018 (up to approximately 23 months)
Adverse Event Reporting Description	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.
Arm/Group Title	Pembrolizumab-China Extension		Chemotherapy (SOC Treatment)-China Extension
Arm/Group Description	Participants received pembrolizumab 200 mg by IV infusion on Day 1 every 3 weeks (Q3W) for a maximum of 35 cycles (21-day cycles)		Participants received 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 received optional additional maintenance treatment with pemetrexed 500 mg/m^2 by IV infusion on Day 1 Q3W
All Cause Mortality
	Pembrolizumab-China Extension		Chemotherapy (SOC Treatment)-China Extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	50/128 (39.1%)		71/125 (56.8%)
Serious Adverse Events
	Pembrolizumab-China Extension		Chemotherapy (SOC Treatment)-China Extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/128 (29.7%)		40/125 (32%)
Blood and lymphatic system disorders
Agranulocytosis	0/128 (0%)	0	1/125 (0.8%)	1
Anaemia	0/128 (0%)	0	5/125 (4%)	5
Coagulopathy	1/128 (0.8%)	1	0/125 (0%)	0
Lymphadenopathy	0/128 (0%)	0	1/125 (0.8%)	1
Neutropenia	0/128 (0%)	0	1/125 (0.8%)	1
Thrombocytopenia	1/128 (0.8%)	1	0/125 (0%)	0
Cardiac disorders
Acute left ventricular failure	1/128 (0.8%)	1	0/125 (0%)	0
Arteriosclerosis coronary artery	1/128 (0.8%)	1	0/125 (0%)	0
Coronary artery disease	1/128 (0.8%)	1	0/125 (0%)	0
Myocardial infarction	1/128 (0.8%)	1	0/125 (0%)	0
Endocrine disorders
Hyperthyroidism	1/128 (0.8%)	1	0/125 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/128 (0.8%)	1	1/125 (0.8%)	1
Lower gastrointestinal haemorrhage	1/128 (0.8%)	1	0/125 (0%)	0
General disorders
Death	0/128 (0%)	0	2/125 (1.6%)	2
Fatigue	0/128 (0%)	0	1/125 (0.8%)	1
Malaise	0/128 (0%)	0	1/125 (0.8%)	1
Pyrexia	2/128 (1.6%)	2	1/125 (0.8%)	1
Hepatobiliary disorders
Autoimmune hepatitis	2/128 (1.6%)	2	0/125 (0%)	0
Cholelithiasis	1/128 (0.8%)	1	0/125 (0%)	0
Immune system disorders
Anaphylactic reaction	0/128 (0%)	0	1/125 (0.8%)	1
Infections and infestations
Infection	1/128 (0.8%)	1	0/125 (0%)	0
Lung abscess	0/128 (0%)	0	1/125 (0.8%)	1
Lung infection	1/128 (0.8%)	1	1/125 (0.8%)	1
Pneumonia	8/128 (6.3%)	8	10/125 (8%)	12
Pulmonary tuberculosis	1/128 (0.8%)	1	1/125 (0.8%)	1
Septic shock	0/128 (0%)	0	2/125 (1.6%)	2
Upper respiratory tract infection	1/128 (0.8%)	1	1/125 (0.8%)	1
Injury, poisoning and procedural complications
Craniocerebral injury	1/128 (0.8%)	1	0/125 (0%)	0
Subdural haematoma	1/128 (0.8%)	1	0/125 (0%)	0
Investigations
Blood creatinine increased	1/128 (0.8%)	1	1/125 (0.8%)	1
Neutrophil count decreased	0/128 (0%)	0	1/125 (0.8%)	1
Platelet count decreased	0/128 (0%)	0	3/125 (2.4%)	4
White blood cell count decreased	0/128 (0%)	0	1/125 (0.8%)	1
Metabolism and nutrition disorders
Decreased appetite	0/128 (0%)	0	2/125 (1.6%)	2
Diabetes mellitus	1/128 (0.8%)	1	0/125 (0%)	0
Electrolyte imbalance	0/128 (0%)	0	1/125 (0.8%)	1
Hyperuricaemia	2/128 (1.6%)	2	1/125 (0.8%)	2
Hypoalbuminaemia	1/128 (0.8%)	1	0/125 (0%)	0
Ketoacidosis	0/128 (0%)	0	1/125 (0.8%)	1
Musculoskeletal and connective tissue disorders
Bone pain	0/128 (0%)	0	1/125 (0.8%)	1
Joint range of motion decreased	1/128 (0.8%)	1	0/125 (0%)	0
Neck pain	0/128 (0%)	0	1/125 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone	1/128 (0.8%)	1	0/125 (0%)	0
Oesophageal carcinoma	2/128 (1.6%)	2	0/125 (0%)	0
Nervous system disorders
Cerebral infarction	1/128 (0.8%)	1	0/125 (0%)	0
Dizziness	1/128 (0.8%)	1	0/125 (0%)	0
Haemorrhage intracranial	1/128 (0.8%)	1	0/125 (0%)	0
VIth nerve disorder	0/128 (0%)	0	1/125 (0.8%)	1
Renal and urinary disorders
Haematuria	1/128 (0.8%)	1	0/125 (0%)	0
Renal failure	1/128 (0.8%)	1	0/125 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/128 (0%)	0	1/125 (0.8%)	1
Cough	1/128 (0.8%)	1	1/125 (0.8%)	1
Haemoptysis	2/128 (1.6%)	2	0/125 (0%)	0
Interstitial lung disease	4/128 (3.1%)	5	0/125 (0%)	0
Pleural effusion	1/128 (0.8%)	1	0/125 (0%)	0
Productive cough	1/128 (0.8%)	1	0/125 (0%)	0
Pulmonary embolism	2/128 (1.6%)	2	3/125 (2.4%)	3
Respiratory failure	1/128 (0.8%)	1	1/125 (0.8%)	1
Skin and subcutaneous tissue disorders
Drug eruption	0/128 (0%)	0	1/125 (0.8%)	2
Eczema	1/128 (0.8%)	1	0/125 (0%)	0
Urticaria	0/128 (0%)	0	1/125 (0.8%)	1
Vascular disorders
Superior vena cava syndrome	0/128 (0%)	0	1/125 (0.8%)	1
Other (Not Including Serious) Adverse Events
	Pembrolizumab-China Extension		Chemotherapy (SOC Treatment)-China Extension
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	116/128 (90.6%)		119/125 (95.2%)
Blood and lymphatic system disorders
Anaemia	36/128 (28.1%)	41	70/125 (56%)	110
Leukopenia	2/128 (1.6%)	2	16/125 (12.8%)	43
Neutropenia	0/128 (0%)	0	15/125 (12%)	25
Endocrine disorders
Hyperthyroidism	7/128 (5.5%)	8	0/125 (0%)	0
Hypothyroidism	15/128 (11.7%)	18	0/125 (0%)	0
Gastrointestinal disorders
Abdominal distension	5/128 (3.9%)	5	8/125 (6.4%)	9
Abdominal pain	2/128 (1.6%)	2	7/125 (5.6%)	7
Constipation	17/128 (13.3%)	19	30/125 (24%)	37
Diarrhoea	7/128 (5.5%)	12	13/125 (10.4%)	14
Nausea	10/128 (7.8%)	12	24/125 (19.2%)	36
Vomiting	9/128 (7%)	10	17/125 (13.6%)	22
General disorders
Asthenia	5/128 (3.9%)	6	11/125 (8.8%)	12
Chest discomfort	7/128 (5.5%)	8	7/125 (5.6%)	8
Chest pain	6/128 (4.7%)	8	15/125 (12%)	16
Fatigue	10/128 (7.8%)	13	20/125 (16%)	37
Malaise	6/128 (4.7%)	6	16/125 (12.8%)	17
Pyrexia	28/128 (21.9%)	41	22/125 (17.6%)	23
Infections and infestations
Nasopharyngitis	14/128 (10.9%)	16	4/125 (3.2%)	5
Upper respiratory tract infection	16/128 (12.5%)	21	9/125 (7.2%)	10
Investigations
Alanine aminotransferase increased	27/128 (21.1%)	40	31/125 (24.8%)	55
Aspartate aminotransferase increased	27/128 (21.1%)	37	26/125 (20.8%)	44
Bilirubin conjugated increased	9/128 (7%)	12	3/125 (2.4%)	7
Blood albumin decreased	4/128 (3.1%)	5	8/125 (6.4%)	9
Blood bilirubin increased	12/128 (9.4%)	15	7/125 (5.6%)	9
Blood thyroid stimulating hormone increased	7/128 (5.5%)	8	4/125 (3.2%)	7
Blood uric acid increased	7/128 (5.5%)	8	0/125 (0%)	0
Gamma-glutamyltransferase increased	14/128 (10.9%)	18	11/125 (8.8%)	20
Neutrophil count decreased	3/128 (2.3%)	3	69/125 (55.2%)	227
Platelet count decreased	5/128 (3.9%)	6	29/125 (23.2%)	83
Weight decreased	17/128 (13.3%)	18	15/125 (12%)	19
White blood cell count decreased	5/128 (3.9%)	6	63/125 (50.4%)	240
Metabolism and nutrition disorders
Decreased appetite	23/128 (18%)	24	38/125 (30.4%)	66
Hyperglycaemia	12/128 (9.4%)	12	7/125 (5.6%)	9
Hyperuricaemia	8/128 (6.3%)	14	5/125 (4%)	7
Hypoalbuminaemia	17/128 (13.3%)	21	18/125 (14.4%)	21
Hypocalcaemia	10/128 (7.8%)	10	1/125 (0.8%)	1
Hypokalaemia	17/128 (13.3%)	23	11/125 (8.8%)	17
Hyponatraemia	13/128 (10.2%)	21	12/125 (9.6%)	17
Hypoproteinaemia	12/128 (9.4%)	16	10/125 (8%)	14
Musculoskeletal and connective tissue disorders
Arthralgia	12/128 (9.4%)	17	11/125 (8.8%)	20
Back pain	12/128 (9.4%)	22	9/125 (7.2%)	10
Musculoskeletal pain	11/128 (8.6%)	15	5/125 (4%)	5
Myalgia	4/128 (3.1%)	4	9/125 (7.2%)	13
Pain in extremity	7/128 (5.5%)	9	13/125 (10.4%)	16
Nervous system disorders
Dizziness	8/128 (6.3%)	9	5/125 (4%)	5
Hypoaesthesia	3/128 (2.3%)	3	11/125 (8.8%)	13
Psychiatric disorders
Insomnia	11/128 (8.6%)	15	12/125 (9.6%)	13
Respiratory, thoracic and mediastinal disorders
Cough	25/128 (19.5%)	28	18/125 (14.4%)	18
Dyspnoea	15/128 (11.7%)	16	16/125 (12.8%)	16
Haemoptysis	21/128 (16.4%)	26	10/125 (8%)	11
Productive cough	7/128 (5.5%)	10	6/125 (4.8%)	6
Skin and subcutaneous tissue disorders
Alopecia	1/128 (0.8%)	1	32/125 (25.6%)	33
Pruritus	17/128 (13.3%)	26	3/125 (2.4%)	3
Rash	22/128 (17.2%)	25	6/125 (4.8%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.