Efficacy and Safety Study of Pembrolizumab (MK-3475) With... | NCT04676412

NCT04676412

ID	Type	Description
MK-7902-007	Other Identifier	MSD
E7080-G000-314	Other Identifier	Eisai Protocol Number
LEAP-007	Other Identifier	MSD

Status Module

Sponsor/Collaborators Module

Name	Class
Eisai Inc.	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Pembrolizumab + Lenvatinib	Experimental	Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.	Biological: Pembrolizumab Drug: Lenvatinib
Pembrolizumab + Placebo	Active Comparator	Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.	Biological: Pembrolizumab Drug: Placebo for lenvatinib

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	IV infusion	Pembrolizumab + Lenvatinib Pembrolizumab + Placebo

Outcomes Module

Primary Outcomes

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)	PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data were from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by BICR per RECIST 1.1 was presented.	Up to approximately 18 months
Overall Survival (OS)	OS was defined as the time from date of randomization to date of death from any cause.	Up to approximately 18 months

Secondary Outcomes

Measure	Description	Time Frame
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	ORR was defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experienced CR or PR as assessed by BICR were presented.	Up to approximately 18 months

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC])
Has measurable disease based on Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1)
Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory
Has a life expectancy of ≥3 months
Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization
Male participants must agree to the following during the treatment period and for ≥7 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause)
Female participants are eligible to participate if not pregnant or breastfeeding, and ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR 2) Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/matching placebo, whichever occurs last
Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization
Has adequate organ function

Exclusion Criteria:

Has known untreated central nervous system metastases and/or carcinomatous meningitis
Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.)
Has radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
Has an active autoimmune disease that has required systemic treatment in the past 2 years Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
Has had an allogeneic tissue/solid organ transplant
Has a known history of human immunodeficiency virus (HIV) infection
Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease
Has a known history of hepatitis B or known active hepatitis C virus infection
Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption
Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability
Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment
Has a known history of active tuberculosis (TB)
Has an active infection requiring systemic therapy
Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab
Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC
Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents
Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)
Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment
Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment
Has received a live vaccine within 30 days before the first dose of study treatment
Has had major surgery within 3 weeks prior to first dose of study treatment
Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula

Contacts/Locations Module

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

Facility	Status	City	State	ZIP	Country	Contacts
Anhui Provincial Hospital ( Site 0108)		Hefei	Anhui	230001	China
The First Affiliated Hospital of Anhui Medical University ( Site 0113)

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
38159809	Result	Yang JC, Han B, De La Mora Jimenez E, Lee JS, Koralewski P, Karadurmus N, Sugawara S, Livi L, Basappa NS, Quantin X, Dudnik J, Ortiz DM, Mekhail T, Okpara CE, Dutcus C, Zimmer Z, Samkari A, Bhagwati N, Csoszi T. Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial. J Thorac Oncol. 2024 Jun;19(6):941-953. doi: 10.1016/j.jtho.2023.12.023. Epub 2023 Dec 29.

Label	URL
Merck Clinical Trials Information	View source

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

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	Aug 18, 2022

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion.

Arm/Group Information

ID	Title	Description
BG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
BG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

Years

Title

Denominators

Categories

Title	Measurements
	BG00064.2± 8.2 BG00164.2± 7.6 BG00264.2± 7.8

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0007 BG00110 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Eastern Cooperative Oncology Group (ECOG) Performance Status

Randomization of participants in the study was stratified by an ECOG Performance Status of 0 (Fully active, able to carry on all pre-disease performance without restriction) or 1 (Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature).

Count of Participants

Participants

Title

Denominators

Categories

ECOG=0

Title	Measurements
	BG0006 BG001

Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline

Participants were assessed for their PD-L1 tumor expression level by immunohistochemistry assay using tumor tissue from a newly obtained biopsy. Randomization of participants in the study was stratified by PD-L1 tumor proportion score (TPS) at baseline (1-49% or ≥ 50%). Higher percentages of PD-L1 TPS staining correspond to higher positivity of PD-L1 on a tumor.

Count of Participants

Participants

Title

Denominators

Categories

TPS=1-49%

Title	Measurements
	BG00021 BG001

Geographic Region

Randomization of participants in this study was stratified by geographic region of the enrolling site (East Asia or non-East Asia).

Count of Participants

Participants

Title

Denominators

Categories

East Asia

Title	Measurements
	BG00049 BG00158

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

Secondary

Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

ORR was defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experienced CR or PR as assessed by BICR were presented.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion that were evaluable for response.

Posted

Number

95% Confidence Interval

Percentage of participants

Up to approximately 18 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Units	Counts
Participants	OG00042 OG00153

Title

Denominators

Categories

Title	Measurements
	OG00033.3(19.6 to 49.5) OG00139.6(26.5 to 54.0)

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		Stratified Miettinen and Nurminen	One-sided p-value for testing. H0: difference in percentage =0 versus H1: difference in percentage > 0	0.79262		Difference in percentage	-8.4			2-Sided	95	-27.4	11.9					Other	Percent difference and 95% CI were calculated using Miettinen and Nurminen method with Efron's method of tie handling with treatment as a covariate stratified by ECOG performance status (0 versus 1), geographic region of the enrolling site (East Asia versus non-East Asia), and baseline PD-L1 status (1-49% versus ≥50%).

Secondary

Number of Participants Who Experienced an Adverse Event (AE)

An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced an AE were reported.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion who received at least one dose of study treatment.

Posted

Count of Participants

Participants

Up to approximately 52 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Number of Participants Who Discontinued Study Treatment Due to an AE

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion who received at least one dose of study treatment

Posted

Count of Participants

Participants

Up to approximately 30 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score

EORTC QLQ-C30 is a questionnaire to assess the overall quality of life (QoL) of cancer patients. Participant responses to questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and QoL ("How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) is computed by averaging the raw scores of the 2 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in GHS and QoL combined score was presented.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion who received at least one dose of treatment and had at least one EORTC-QLQ-C30 assessment data available.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and Week 21

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion who received at least one dose of treatment and had at least one assessment for EORTC QLQ-LC13 available.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and Week 21

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score

The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in chest pain (EORTC QLQ-LC13 Item 40) score was reported. A lower score indicated a better outcome.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion who received at least one dose of treatment and had at least one EORTC QLQ-LC13 assessment data available.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and Week 21

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in dyspnea (EORTC QLQ-C30 Item 8) score was reported. A lower score indicated a better outcome.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and Week 21

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-C30 physical functioning (Items 1-5) combined score was presented.

Posted

Least Squares Mean

95% Confidence Interval

Score on a scale

Baseline and Week 21

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo

Secondary

Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status /Quality of Life (Items 29 & 30) Scale Combined Score

EORTC QLQ-C30 is a questionnaire to assess QoL of cancer patients. Participant responses to questions on GHS ("How would you rate your overall health during the past week?") and QoL ("How would you rate your overall QoL during the past week?") were scored on a 7-point scale (1= Very poor to 7=Excellent). The combined score of GHS (Item 29) and QoL (Item 30) was computed by averaging raw scores of the 2 items and applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in GHS-QoL combined score. A longer TTD indicates a better outcome.

Posted

Median

95% Confidence Interval

Months

Up to approximately 25 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score

EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question: "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0-100. A lower score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 31). A longer TTD indicates a better outcome.

Posted

Median

95% Confidence Interval

Months

Up to approximately 25 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score

EORTC QLQ-LC13 is a lung cancer specific questionnaire. Participant responses to the question: "Have you had pain in your chest?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0-100. A lower score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in cough (Item 40). A longer TTD indicates a better outcome.

Posted

Median

95% Confidence Interval

Months

Up to approximately 25 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to the question: "Were you short of breath?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. A lower score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in dyspnea (Item 8). A longer TTD indicates a better outcome.

Posted

Median

95% Confidence Interval

Months

Up to approximately 25 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Time to True Deterioration (TTD) in the Composite Endpoint of EORTC QLQ-LC13 Cough (Item 31), EORTC QLQ-LC13 Chest Pain (Item 40), or EORTC QLQ-C30 Dyspnea (Item 8)

The EORTC QLQ-C30 is a 30-item questionnaire developed to assess the QoL of cancer patients, including a single-item scale score for dyspnea (Item 8; score range:1=Not at All to 4=Very Much). Used in combination with QLQ-C30, the EORTC QLQ-LC13 is a supplemental lung cancer-specific module, including a single-item scale score for cough (Item 31; score range:1=Not at All to 4=Very Much ) and chest pain (Item 40, score range: 1=Not at All to 4=Very Much). The combined score of items 31, 40 and 8 was computed by averaging the raw scores of the items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. The TTD in the composite endpoint of EORTC QLQ-LC13 Item 31, EORTC QLQ-LC13 Item 40, EORTC QLQ-C30 Item 8 scale score was presented, defined as the time to first onset of a ≥10point decrease from baseline in anyone of the three scale items. A longer TTD indicates better outcome.

Posted

Median

95% Confidence Interval

Months

Up to approximately 25 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Secondary

Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

EORTC QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. Participant responses to 5 questions about their physical functioning (Items 1 to 5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. TTD was defined as the time from baseline to first onset of ≥10-point negative change (decrease) from baseline in physical functioning (Items 1 to 5). A longer TTD indicates a better outcome.

Posted

Median

95% Confidence Interval

Months

Up to approximately 25 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001

Primary

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)

PFS was defined as the time from date of randomization to the date of the first documentation of progressive disease (PD) or death from any cause, whichever occurred first. Per RECIST 1.1, PD was defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. Data were from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by BICR per RECIST 1.1 was presented.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion that were evaluable for response.

Posted

Median

95% Confidence Interval

Months

Up to approximately 18 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo

Primary

Overall Survival (OS)

OS was defined as the time from date of randomization to date of death from any cause.

All Chinese participants who were randomized to the global study (NCT03829332) or to the extension portion that were evaluable for response.

Posted

Median

95% Confidence Interval

Months

Up to approximately 18 months

ID	Title	Description
OG000	Pembrolizumab + Lenvatinib	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.
OG001	Pembrolizumab + Placebo	Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Lenvatinib + Pembrolizumab	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued lenvatinib and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.	28	49	24	49	49	49
EG001	Placebo + Pembrolizumab	Participants received pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.	32	58	17	58	54	58

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac failure acute	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Immune-mediated myocarditis	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Colitis	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0012 events1 affected58 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0010 events0 affected58 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 events2 affected49 at risk EG0011 events1 affected58 at risk
Asthenia	General disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Chest discomfort	General disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0010 events0 affected58 at risk
Death	General disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0011 events1 affected58 at risk
Fatigue	General disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Hepatitis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Immune-mediated hepatitis	Hepatobiliary disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0004 events4 affected49 at risk EG0014 events4 affected58 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0010 events0 affected58 at risk
Amylase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0010 events0 affected58 at risk
Coagulation time prolonged	Investigations	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0010 events0 affected58 at risk
Hypercalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0003 events1 affected49 at risk EG0010 events0 affected58 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Pathological fracture	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Altered state of consciousness	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Brain injury	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Cerebral infarction	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0012 events2 affected58 at risk
Chronic respiratory disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0004 events4 affected49 at risk EG0011 events1 affected58 at risk
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0011 events1 affected58 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0010 events0 affected58 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0011 events1 affected58 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk
Immune-mediated dermatitis	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0011 events1 affected58 at risk
Hypotension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0010 events0 affected58 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 26.1	Systematic Assessment	EG00021 events14 affected49 at risk EG00131 events16 affected58 at risk
Arrhythmia	Cardiac disorders	MedDRA 26.1	Systematic Assessment	EG0004 events4 affected49 at risk EG0014 events3 affected58 at risk
Hyperthyroidism	Endocrine disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG00112 events8 affected58 at risk
Hypothyroidism	Endocrine disorders	MedDRA 26.1	Systematic Assessment	EG00042 events22 affected49 at risk EG00112 events11 affected58 at risk
Abdominal distension	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0004 events3 affected49 at risk EG0011 events1 affected58 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0007 events6 affected49 at risk EG0015 events5 affected58 at risk
Constipation	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0004 events3 affected49 at risk EG0017 events6 affected58 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00038 events20 affected49 at risk EG0019 events8 affected58 at risk
Nausea	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0004 events3 affected49 at risk EG0014 events4 affected58 at risk
Stomatitis	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG00010 events5 affected49 at risk EG0010 events0 affected58 at risk
Vomiting	Gastrointestinal disorders	MedDRA 26.1	Systematic Assessment	EG0008 events6 affected49 at risk EG0018 events5 affected58 at risk
Asthenia	General disorders	MedDRA 26.1	Systematic Assessment	EG0004 events4 affected49 at risk EG0013 events3 affected58 at risk
Chest discomfort	General disorders	MedDRA 26.1	Systematic Assessment	EG0004 events3 affected49 at risk EG0011 events1 affected58 at risk
Chest pain	General disorders	MedDRA 26.1	Systematic Assessment	EG0008 events6 affected49 at risk EG0013 events3 affected58 at risk
Fatigue	General disorders	MedDRA 26.1	Systematic Assessment	EG0005 events5 affected49 at risk EG0012 events2 affected58 at risk
Malaise	General disorders	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0011 events1 affected58 at risk
Pyrexia	General disorders	MedDRA 26.1	Systematic Assessment	EG00013 events10 affected49 at risk EG00114 events11 affected58 at risk
COVID-19	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0014 events4 affected58 at risk
Nasopharyngitis	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0011 events1 affected58 at risk
Pneumonia	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0006 events6 affected49 at risk EG0017 events5 affected58 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0014 events4 affected58 at risk
Urinary tract infection	Infections and infestations	MedDRA 26.1	Systematic Assessment	EG00016 events6 affected49 at risk EG00119 events8 affected58 at risk
Alanine aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00021 events14 affected49 at risk EG00121 events13 affected58 at risk
Amylase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00012 events6 affected49 at risk EG0017 events3 affected58 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00027 events17 affected49 at risk EG00127 events16 affected58 at risk
Bilirubin conjugated increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00012 events4 affected49 at risk EG0015 events4 affected58 at risk
Blood alkaline phosphatase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0006 events5 affected49 at risk EG0011 events1 affected58 at risk
Blood bilirubin increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00018 events9 affected49 at risk EG00112 events6 affected58 at risk
Blood creatinine increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0007 events6 affected49 at risk EG0016 events5 affected58 at risk
Blood glucose increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0006 events4 affected49 at risk EG0010 events0 affected58 at risk
Blood thyroid stimulating hormone decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0001 events1 affected49 at risk EG0014 events4 affected58 at risk
Blood thyroid stimulating hormone increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00015 events12 affected49 at risk EG0012 events1 affected58 at risk
Blood urea increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00011 events6 affected49 at risk EG0010 events0 affected58 at risk
Blood urine present	Investigations	MedDRA 26.1	Systematic Assessment	EG0007 events3 affected49 at risk EG0011 events1 affected58 at risk
Gamma-glutamyltransferase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0008 events5 affected49 at risk EG0015 events3 affected58 at risk
Lipase increased	Investigations	MedDRA 26.1	Systematic Assessment	EG00012 events6 affected49 at risk EG0013 events2 affected58 at risk
Neutrophil count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0005 events4 affected49 at risk EG0011 events1 affected58 at risk
Platelet count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG00019 events13 affected49 at risk EG00130 events4 affected58 at risk
Protein urine present	Investigations	MedDRA 26.1	Systematic Assessment	EG0005 events3 affected49 at risk EG0014 events1 affected58 at risk
Urinary occult blood positive	Investigations	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0019 events3 affected58 at risk
Weight decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG00027 events21 affected49 at risk EG0013 events2 affected58 at risk
Weight increased	Investigations	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG00117 events11 affected58 at risk
White blood cell count decreased	Investigations	MedDRA 26.1	Systematic Assessment	EG0008 events6 affected49 at risk EG0012 events2 affected58 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG00019 events14 affected49 at risk EG00110 events8 affected58 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG00014 events7 affected49 at risk EG0015 events5 affected58 at risk
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0005 events3 affected49 at risk EG0011 events1 affected58 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0004 events3 affected49 at risk EG0016 events1 affected58 at risk
Hyperuricaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0008 events4 affected49 at risk EG0014 events4 affected58 at risk
Hypoalbuminaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG00012 events10 affected49 at risk EG00115 events8 affected58 at risk
Hypocalcaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0004 events4 affected49 at risk EG0013 events2 affected58 at risk
Hypokalaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0007 events6 affected49 at risk EG0019 events7 affected58 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0008 events8 affected49 at risk EG0017 events6 affected58 at risk
Hypophosphataemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0000 events0 affected49 at risk EG0015 events3 affected58 at risk
Hypoproteinaemia	Metabolism and nutrition disorders	MedDRA 26.1	Systematic Assessment	EG0005 events5 affected49 at risk EG0013 events3 affected58 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG00010 events5 affected49 at risk EG0014 events3 affected58 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0006 events5 affected49 at risk EG0013 events3 affected58 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 26.1	Systematic Assessment	EG0008 events6 affected49 at risk EG0013 events3 affected58 at risk
Dizziness	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0002 events1 affected49 at risk EG0014 events4 affected58 at risk
Headache	Nervous system disorders	MedDRA 26.1	Systematic Assessment	EG0005 events3 affected49 at risk EG0010 events0 affected58 at risk
Insomnia	Psychiatric disorders	MedDRA 26.1	Systematic Assessment	EG0005 events5 affected49 at risk EG0013 events3 affected58 at risk
Haematuria	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG00015 events10 affected49 at risk EG00116 events10 affected58 at risk
Proteinuria	Renal and urinary disorders	MedDRA 26.1	Systematic Assessment	EG00048 events26 affected49 at risk EG00119 events11 affected58 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0006 events5 affected49 at risk EG0019 events7 affected58 at risk
Dysphonia	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0012 events2 affected58 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0005 events5 affected49 at risk EG0011 events1 affected58 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0003 events3 affected49 at risk EG0010 events0 affected58 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0008 events7 affected49 at risk EG00126 events10 affected58 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA 26.1	Systematic Assessment	EG0002 events2 affected49 at risk EG0014 events3 affected58 at risk
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG00010 events9 affected49 at risk EG0011 events1 affected58 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG00011 events9 affected49 at risk EG0014 events4 affected58 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 26.1	Systematic Assessment	EG00021 events13 affected49 at risk EG00110 events7 affected58 at risk
Hypertension	Vascular disorders	MedDRA 26.1	Systematic Assessment	EG00023 events21 affected49 at risk EG0017 events7 affected58 at risk

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

Ancestor Terms

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
C531958	lenvatinib

Participants received pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity. As of 30-Jul-2021, participants discontinued placebo and participants who remained on treatment received open-label pembrolizumab only at same dose and schedule.

Units	Counts
Participants	OG00042 OG00153