Study of Pembrolizumab (MK-3475) Versus Platinum-Based Ch... | NCT02220894

ID	Type	Description
152877	Registry Identifier	JAPIC-CTI
MK-3475-042	Other Identifier	Merck Protocol Number
KEYNOTE-042	Other Identifier	Merck
2014-001473-14	EudraCT Number

Label	Type	Description	Intervention Names
Pembrolizumab	Experimental	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
SOC Treatment	Active Comparator	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 Drug: paclitaxel Drug: pemetrexed

Name	Type	Description	Arm Group Labels	Other Names
pembrolizumab	Biological		Pembrolizumab	MK-3475 KEYTRUDA®

Measure	Description	Time Frame
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥50%	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.	Up to approximately 44 months
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥20%	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.	Up to approximately 44 months
Overall Survival (OS) in Participants With a Tumor Proportion Score (TPS) of ≥1%	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.

Measure	Description	Time Frame
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%	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.

Eligibility Module

Eligibility Criteria

Inclusion criteria:

Histologically- or cytologically-confirmed diagnosis of advanced or metastatic NSCLC
PD-L1 positive tumor
Measureable 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 child-bearing 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-PD-L2, 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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
36306479	Derived	de Castro G Jr, Kudaba I, Wu YL, Lopes G, Kowalski DM, Turna HZ, Caglevic C, Zhang L, Karaszewska B, Laktionov KK, Srimuninnimit V, Bondarenko I, Kubota K, Mukherjee R, Lin J, Souza F, Mok TSK, Cho BC. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy as First-Line Therapy in Patients With Non-Small-Cell Lung Cancer and Programmed Death Ligand-1 Tumor Proportion Score >/= 1% in the KEYNOTE-042 Study. J Clin Oncol. 2023 Apr 10;41(11):1986-1991. doi: 10.1200/JCO.21.02885. Epub 2022 Oct 28.
35073727

Label	URL
Merck Clinical Trials Information	View source

ID	Title	Description
FG000	Pembrolizumab	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.
FG001

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 24, 2021

ID	Title	Description
BG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
BG001	Chemotherapy (SOC Treatment)	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
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG000637 BG001637 BG0021274

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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

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.

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

Posted

Median

95% Confidence Interval

Months

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Units	Counts
Participants	OG000299 OG001300

Title

Denominators

Categories

Title	Measurements
	OG00020.0(15.9 to 24.2) OG00112.2(10.4 to 14.6)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Log Rank		0.0003	One-sided p-value based on stratified log-rank test	Hazard Ratio (HR)	0.70			2-Sided	95	0.58	0.86			Hazard ratio based on Cox regression model with treatment as a covariate stratified by geographic region (East Asia vs. non-East Asia), ECOG PS (0 vs. 1), and histology (squamous vs. non-squamous).		Superiority

Primary

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

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.

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

Posted

Median

95% Confidence Interval

Months

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Primary

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

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.

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

Posted

Median

95% Confidence Interval

Months

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Secondary

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%

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.

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

Posted

Median

95% Confidence Interval

Months

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001

Secondary

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.

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

Posted

Median

95% Confidence Interval

Months

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001

Secondary

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.

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

Posted

Median

95% Confidence Interval

Months

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001

Secondary

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%

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.

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

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Secondary

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.

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

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Secondary

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.

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

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 44 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Secondary

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

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.

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

Posted

Count of Participants

Participants

Up to approximately 38 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Secondary

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

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.

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

Posted

Count of Participants

Participants

Up to approximately 35 months

ID	Title	Description
OG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)
OG001	Chemotherapy (SOC Treatment)	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

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Agranulocytosis	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG00123 events16 affected615 at risk EG0020 events0 affected34 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0018 events8 affected615 at risk EG0020 events0 affected34 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0016 events6 affected615 at risk EG0020 events0 affected34 at risk
Coronary artery disease	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Myocardial infarction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0005 events5 affected636 at risk EG0013 events3 affected615 at risk EG0021 events1 affected34 at risk
Death	General disorders	MedDRA 25.0	Systematic Assessment	EG0009 events9 affected636 at risk EG0015 events5 affected615 at risk EG0020 events0 affected34 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Malaise	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected636 at risk EG0010 events0 affected615 at risk EG0021 events1 affected34 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Anaphylactic reaction	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Lung abscess	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00054 events49 affected636 at risk EG00141 events34 affected615 at risk EG0022 events2 affected34 at risk
Septic shock	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0014 events4 affected615 at risk EG0020 events0 affected34 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Subdural haematoma	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Neutrophil count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0015 events5 affected615 at risk EG0020 events0 affected34 at risk
Platelet count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0013 events2 affected615 at risk EG0020 events0 affected34 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected636 at risk EG0013 events3 affected615 at risk EG0020 events0 affected34 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0013 events2 affected615 at risk EG0020 events0 affected34 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Ketoacidosis	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Bone pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Malignant neoplasm progression	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Metastases to bone	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0003 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Cerebral infarction	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Dizziness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Haemorrhage intracranial	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Renal failure	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0015 events5 affected615 at risk EG0020 events0 affected34 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0007 events7 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0006 events4 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00016 events14 affected636 at risk EG0017 events5 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00013 events13 affected636 at risk EG00111 events11 affected615 at risk EG0020 events0 affected34 at risk
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected636 at risk EG0014 events4 affected615 at risk EG0020 events0 affected34 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events1 affected615 at risk EG0020 events0 affected34 at risk
Urticaria	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Superior vena cava syndrome	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Lymph gland infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0010 events0 affected615 at risk EG0021 events1 affected34 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG00117 events16 affected615 at risk EG0020 events0 affected34 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Normochromic anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Splenic infarction	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Acute coronary syndrome	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0013 events3 affected615 at risk EG0020 events0 affected34 at risk
Acute myocardial infarction	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Aortic valve stenosis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Arrhythmia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Atrial fibrillation	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Atrial flutter	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cardiac arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cardiac failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Cardiac failure acute	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Cardiac tamponade	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Cardio-respiratory arrest	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cardiopulmonary failure	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Myocarditis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pericardial effusion	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0006 events6 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pericarditis	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Sinus tachycardia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Supraventricular tachycardia	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Ventricular fibrillation	Cardiac disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Vertigo	Ear and labyrinth disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hypophysitis	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hypopituitarism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hypothyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Colitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0006 events6 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Duodenal perforation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Enterocolitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Gastric haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Gastric ulcer haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Gastritis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Gastrointestinal ulcer	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Glossitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Haematemesis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0010 events0 affected615 at risk EG0021 events1 affected34 at risk
Ileus paralytic	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Incarcerated inguinal hernia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Intestinal ischaemia	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Melaena	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Neutropenic colitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Oesophageal fistula	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pancreatic mass	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Rectal ulcer	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Upper gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events1 affected615 at risk EG0021 events1 affected34 at risk
Volvulus	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Accidental death	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Asthenia	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0014 events4 affected615 at risk EG0020 events0 affected34 at risk
General physical health deterioration	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Ill-defined disorder	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Performance status decreased	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Prosthetic cardiac valve thrombosis	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Sudden death	General disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hepatic function abnormal	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hepatitis acute	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hepatitis toxic	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Contrast media allergy	Immune system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Abdominal sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Abscess jaw	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Amoebiasis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Amoebic dysentery	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Anal abscess	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Biliary sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Bronchitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0008 events8 affected636 at risk EG0013 events3 affected615 at risk EG0020 events0 affected34 at risk
COVID-19	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Candida infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cellulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0013 events2 affected615 at risk EG0020 events0 affected34 at risk
Clostridium difficile infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cystitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Device related infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Diverticulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Enterocolitis infectious	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Gastroenteritis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Herpes zoster	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Infectious pleural effusion	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Infective exacerbation of bronchiectasis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Infective exacerbation of chronic obstructive airways disease	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Influenza	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Laryngitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0013 events3 affected615 at risk EG0020 events0 affected34 at risk
Neutropenic sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Oesophageal candidiasis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Peritonitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Pleural infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pneumocystis jirovecii pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pneumonia aspiration	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pneumonia bacterial	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0012 events2 affected615 at risk EG0021 events1 affected34 at risk
Pneumonia klebsiella	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Post procedural cellulitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pseudomembranous colitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Sepsis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected636 at risk EG0014 events3 affected615 at risk EG0020 events0 affected34 at risk
Urinary tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Vascular access site infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Viral infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cervical vertebral fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Lumbar vertebral fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Subdural haemorrhage	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0010 events0 affected615 at risk EG0021 events1 affected34 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Bilirubin conjugated increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Blood bilirubin increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Blood calcium decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Blood pressure increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Blood prolactin increased	Investigations	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Type 2 diabetes mellitus	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Osteitis	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Osteoporotic fracture	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Rotator cuff syndrome	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Adenocarcinoma gastric	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Anogenital warts	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Cancer pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Gastric cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Infected neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Keratoacanthoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Lung cancer metastatic	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Lung neoplasm malignant	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Squamous cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Squamous cell carcinoma of the tongue	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Tumour associated fever	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0021 events1 affected34 at risk
Tumour necrosis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Altered state of consciousness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Ataxia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Cerebrovascular accident	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0013 events3 affected615 at risk EG0020 events0 affected34 at risk
Coma	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Embolic stroke	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Epilepsy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Ischaemic stroke	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Loss of consciousness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Metabolic encephalopathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Psychomotor hyperactivity	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Seizure	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0013 events2 affected615 at risk EG0020 events0 affected34 at risk
Spinal cord compression	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Syncope	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Completed suicide	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Confusional state	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Delirium	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Depression	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0014 events4 affected615 at risk EG0020 events0 affected34 at risk
Glomerulonephritis membranous	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hydronephrosis	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Nephritis	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Nephropathy	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Renal tubular necrosis	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Urinary retention	Renal and urinary disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Benign prostatic hyperplasia	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Ovarian cyst torsion	Reproductive system and breast disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Acute pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Acute respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Atelectasis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Bronchitis chronic	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Chronic respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0008 events7 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Hydrothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Lung disorder	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Oesophagobronchial fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pleurisy	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00026 events25 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0003 events3 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary artery thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary fistula	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0004 events4 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary oedema	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Pulmonary thrombosis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk
Tracheal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0021 events1 affected34 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Aortic aneurysm	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Arterial thrombosis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Deep vein thrombosis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Embolism	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0002 events2 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Hypotension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Jugular vein thrombosis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0011 events1 affected615 at risk EG0020 events0 affected34 at risk
Peripheral artery occlusion	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Peripheral ischaemia	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0001 events1 affected636 at risk EG0010 events0 affected615 at risk EG0020 events0 affected34 at risk
Venous thrombosis	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG0000 events0 affected636 at risk EG0012 events2 affected615 at risk EG0020 events0 affected34 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG000124 events102 affected636 at risk EG001332 events253 affected615 at risk EG0022 events2 affected34 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG00017 events10 affected636 at risk EG00163 events35 affected615 at risk EG0021 events1 affected34 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0009 events6 affected636 at risk EG001177 events85 affected615 at risk EG0020 events0 affected34 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 25.0	Systematic Assessment	EG0007 events6 affected636 at risk EG00186 events59 affected615 at risk EG0020 events0 affected34 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG00038 events37 affected636 at risk EG0014 events4 affected615 at risk EG0021 events1 affected34 at risk
Hypothyroidism	Endocrine disorders	MedDRA 25.0	Systematic Assessment	EG00099 events76 affected636 at risk EG00110 events10 affected615 at risk EG0025 events3 affected34 at risk
Constipation	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00098 events78 affected636 at risk EG001168 events131 affected615 at risk EG0023 events3 affected34 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00094 events74 affected636 at risk EG001107 events78 affected615 at risk EG0025 events3 affected34 at risk
Nausea	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00098 events73 affected636 at risk EG001407 events195 affected615 at risk EG0021 events1 affected34 at risk
Vomiting	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00062 events50 affected636 at risk EG001167 events106 affected615 at risk EG0020 events0 affected34 at risk
Asthenia	General disorders	MedDRA 25.0	Systematic Assessment	EG00092 events69 affected636 at risk EG001110 events81 affected615 at risk EG0023 events2 affected34 at risk
Chest pain	General disorders	MedDRA 25.0	Systematic Assessment	EG00061 events56 affected636 at risk EG00152 events43 affected615 at risk EG0021 events1 affected34 at risk
Fatigue	General disorders	MedDRA 25.0	Systematic Assessment	EG000129 events101 affected636 at risk EG001193 events129 affected615 at risk EG0020 events0 affected34 at risk
Malaise	General disorders	MedDRA 25.0	Systematic Assessment	EG00015 events15 affected636 at risk EG00149 events32 affected615 at risk EG0021 events1 affected34 at risk
Pyrexia	General disorders	MedDRA 25.0	Systematic Assessment	EG00082 events64 affected636 at risk EG00163 events52 affected615 at risk EG0021 events1 affected34 at risk
Pneumonia	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00040 events39 affected636 at risk EG00135 events30 affected615 at risk EG0021 events1 affected34 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00062 events46 affected636 at risk EG00141 events32 affected615 at risk EG0021 events1 affected34 at risk
Alanine aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00089 events66 affected636 at risk EG00197 events72 affected615 at risk EG0024 events3 affected34 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00083 events62 affected636 at risk EG00187 events57 affected615 at risk EG0023 events3 affected34 at risk
Neutrophil count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0006 events6 affected636 at risk EG001239 events89 affected615 at risk EG0020 events0 affected34 at risk
Platelet count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0007 events7 affected636 at risk EG001144 events65 affected615 at risk EG0020 events0 affected34 at risk
Weight decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG00071 events67 affected636 at risk EG00149 events48 affected615 at risk EG0024 events4 affected34 at risk
White blood cell count decreased	Investigations	MedDRA 25.0	Systematic Assessment	EG0007 events5 affected636 at risk EG001228 events77 affected615 at risk EG0021 events1 affected34 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG000127 events108 affected636 at risk EG001209 events134 affected615 at risk EG0023 events3 affected34 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 25.0	Systematic Assessment	EG00026 events21 affected636 at risk EG00143 events32 affected615 at risk EG0021 events1 affected34 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG000109 events86 affected636 at risk EG001162 events87 affected615 at risk EG0023 events3 affected34 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00070 events61 affected636 at risk EG00151 events43 affected615 at risk EG0021 events1 affected34 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00037 events32 affected636 at risk EG001135 events70 affected615 at risk EG0021 events1 affected34 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 25.0	Systematic Assessment	EG00036 events31 affected636 at risk EG00140 events34 affected615 at risk EG0020 events0 affected34 at risk
Dizziness	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG00028 events25 affected636 at risk EG00149 events39 affected615 at risk EG0020 events0 affected34 at risk
Insomnia	Psychiatric disorders	MedDRA 25.0	Systematic Assessment	EG00038 events34 affected636 at risk EG00151 events45 affected615 at risk EG0020 events0 affected34 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG000128 events107 affected636 at risk EG00172 events66 affected615 at risk EG0022 events2 affected34 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG000120 events105 affected636 at risk EG00181 events72 affected615 at risk EG0021 events1 affected34 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 25.0	Systematic Assessment	EG00062 events45 affected636 at risk EG00125 events23 affected615 at risk EG0024 events3 affected34 at risk
Alopecia	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG0004 events3 affected636 at risk EG001139 events138 affected615 at risk EG0020 events0 affected34 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG00083 events67 affected636 at risk EG00123 events22 affected615 at risk EG0024 events2 affected34 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 25.0	Systematic Assessment	EG00082 events72 affected636 at risk EG00152 events43 affected615 at risk EG0024 events1 affected34 at risk
Hypertension	Vascular disorders	MedDRA 25.0	Systematic Assessment	EG00049 events41 affected636 at risk EG00117 events14 affected615 at risk EG0021 events1 affected34 at risk
Nasopharyngitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00037 events26 affected636 at risk EG00126 events21 affected615 at risk EG0024 events3 affected34 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 25.0	Systematic Assessment	EG00018 events16 affected636 at risk EG00140 events33 affected615 at risk EG0020 events0 affected34 at risk
Oedema peripheral	General disorders	MedDRA 25.0	Systematic Assessment	EG00033 events32 affected636 at risk EG00150 events36 affected615 at risk EG0021 events1 affected34 at risk
Bronchitis	Infections and infestations	MedDRA 25.0	Systematic Assessment	EG00034 events30 affected636 at risk EG00125 events23 affected615 at risk EG0024 events3 affected34 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 25.0	Systematic Assessment	EG00046 events39 affected636 at risk EG00135 events30 affected615 at risk EG0022 events2 affected34 at risk
Headache	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG00058 events44 affected636 at risk EG00162 events51 affected615 at risk EG0022 events2 affected34 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0006 events5 affected636 at risk EG00162 events52 affected615 at risk EG0020 events0 affected34 at risk
Peripheral sensory neuropathy	Nervous system disorders	MedDRA 25.0	Systematic Assessment	EG0005 events4 affected636 at risk EG00155 events43 affected615 at risk EG0020 events0 affected34 at risk

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C582435	pembrolizumab
D016190	Carboplatin
D017239	Paclitaxel
D000068437	Pemetrexed

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000602	Amino Acids, Peptides, and Proteins
D000600	Amino Acids, Dicarboxylic

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab	Participants received pembrolizumab 200 mg by IV infusion on Day 1 Q3W for a maximum of 35 cycles (21-day cycles)	528	637	261	636	535	636
EG001	Chemotherapy (SOC Treatment)	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.	582	637	193	615	577	615
EG002	Pembrolizumab Second Course	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.	18	34	8	34	21	34