Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Nonsmall Cell Lung Cancer (NSCLC) [MK-7902-007/E7080-G000-314/LEAP-007] - China Extension Study

A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naïve, Metastatic Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT04676412

Acronym

LEAP-007

Enrollment

107

Registered

2020-12-21

Start date

2019-10-23

Completion date

2024-03-29

Last updated

2025-04-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Non-small Cell Lung Cancer

Keywords

programmed cell death 1 (PD-1, PD1), programmed cell death-ligand 1 (PD-L1, PDL1), programmed cell death-ligand 2 (PD-L2, PDL2)

Brief summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%. The primary study hypotheses are that: 1) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1); and 2) the combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).

Detailed description

The main study will have a duration of approximately 5 years and the extension period will have a duration of approximately 1 year. The base study and the China extension to MK-7902-007 (NCT03829332) will enroll a total of approximately 120 Chinese participants. As of 30-Jul-2021, active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue lenvatinib and placebo, and participants who remain on treatment will receive open-label pembrolizumab only.

Interventions

BIOLOGICALPembrolizumab

IV infusion

DRUGLenvatinib

oral capsule

DRUGPlacebo for lenvatinib

oral capsule

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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)	Up to approximately 18 months	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.
Overall Survival (OS)	Up to approximately 18 months	OS was defined as the time from date of randomization to date of death from any cause.

Secondary

Measure	Time frame	Description
Number of Participants Who Discontinued Study Treatment Due to an AE	Up to approximately 30 months	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 discontinued study treatment due to an AE were reported
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	Baseline and Week 21	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.
Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score	Baseline and Week 21	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.
Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score	Baseline and Week 21	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.
Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	Baseline and Week 21	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.
Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	Baseline and Week 21	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.
Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	Up to approximately 18 months	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.
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score	Up to approximately 25 months	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.
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score	Up to approximately 25 months	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.
Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score	Up to approximately 25 months	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.
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)	Up to approximately 25 months	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.
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	Up to approximately 25 months	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.
Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status /Quality of Life (Items 29 & 30) Scale Combined Score	Up to approximately 25 months	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.
Number of Participants Who Experienced an Adverse Event (AE)	Up to approximately 52 months	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.

Countries

China

Participant flow

Pre-assignment details

107 Chinese participants were randomized and received treatment (global study \[NCT03829332; n=80\] or to the extension portion \[n=27\]).

Participants by arm

Arm	Count
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.	49
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.	58
Total	107

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Death	28	31
Overall Study	Lost to Follow-up	1	2
Overall Study	Sponsor Decision	20	23
Overall Study	Withdrawal by Subject	0	2

Baseline characteristics

Characteristic	Pembrolizumab + Lenvatinib	Pembrolizumab + Placebo	Total
Age, Continuous	64.2 Years STANDARD_DEVIATION 8.2	64.2 Years STANDARD_DEVIATION 7.6	64.2 Years STANDARD_DEVIATION 7.8
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG=0	6 Participants	10 Participants	16 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG=1	43 Participants	48 Participants	91 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	49 Participants	58 Participants	107 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Geographic Region East Asia	49 Participants	58 Participants	107 Participants
Geographic Region Non-East Asia	0 Participants	0 Participants	0 Participants
Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline TPS=1-49%	21 Participants	33 Participants	54 Participants
Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline TPS≥ 50%	28 Participants	25 Participants	53 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	49 Participants	58 Participants	107 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	0 Participants	0 Participants	0 Participants
Sex: Female, Male Female	7 Participants	10 Participants	17 Participants
Sex: Female, Male Male	42 Participants	48 Participants	90 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	28 / 49	32 / 58
other Total, other adverse events	49 / 49	54 / 58
serious Total, serious adverse events	24 / 49	17 / 58

Outcome results

Primary

Overall Survival (OS)

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

Time frame: Up to approximately 18 months

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

Arm	Measure	Value (MEDIAN)
Pembrolizumab + Lenvatinib	Overall Survival (OS)	11.4 Months
Pembrolizumab + Placebo	Overall Survival (OS)	NA Months

Comparison: HR and 95% CIs were calculated using Cox regression model 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%).p-value: 0.819795% CI: [0.61, 3.87]Stratified Log Rank

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.

Time frame: Up to approximately 18 months

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

Arm	Measure	Value (MEDIAN)
Pembrolizumab + Lenvatinib	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)	6.1 Months
Pembrolizumab + Placebo	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)	10.3 Months

p-value: 0.7108495% CI: [0.61, 2.25]Stratified Log Rank

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.

Time frame: Baseline and Week 21

Population: 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.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Pembrolizumab + Lenvatinib	Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score	-3.84 Score on a scale
Pembrolizumab + Placebo	Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score	-7.42 Score on a scale

p-value: 0.329895% CI: [-3.7, 10.87]cLDA model

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.

Time frame: Baseline and Week 21

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Pembrolizumab + Lenvatinib	Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score	-2.97 Score on a scale
Pembrolizumab + Placebo	Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score	-11.78 Score on a scale

p-value: 0.062895% CI: [-0.49, 18.11]cLDA model

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.

Time frame: Baseline and Week 21

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Pembrolizumab + Lenvatinib	Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	0.54 Score on a scale
Pembrolizumab + Placebo	Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	0.82 Score on a scale

p-value: 0.959495% CI: [-11.32, 10.75]cLDA model

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.

Time frame: Baseline and Week 21

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Pembrolizumab + Lenvatinib	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	-2.43 Score on a scale
Pembrolizumab + Placebo	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	-2.18 Score on a scale

p-value: 0.951995% CI: [-8.59, 8.09]cLDA model

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.

Time frame: Baseline and Week 21

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Pembrolizumab + Lenvatinib	Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	-5.15 Score on a scale
Pembrolizumab + Placebo	Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	0.38 Score on a scale

p-value: 0.16295% CI: [-13.37, 2.31]cLDA model

Secondary

Number of Participants Who Discontinued Study Treatment Due to an 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 discontinued study treatment due to an AE were reported

Time frame: Up to approximately 30 months

Population: 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

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Pembrolizumab + Lenvatinib	Number of Participants Who Discontinued Study Treatment Due to an AE	19 Participants
Pembrolizumab + Placebo	Number of Participants Who Discontinued Study Treatment Due to an AE	13 Participants

Secondary

Number of Participants Who Experienced an Adverse Event (AE)

Time frame: Up to approximately 52 months

Population: 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.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
Pembrolizumab + Lenvatinib	Number of Participants Who Experienced an Adverse Event (AE)	49 Participants
Pembrolizumab + Placebo	Number of Participants Who Experienced an Adverse Event (AE)	57 Participants

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.

Time frame: Up to approximately 18 months

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

Arm	Measure	Value (NUMBER)
Pembrolizumab + Lenvatinib	Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	33.3 Percentage of participants
Pembrolizumab + Placebo	Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	39.6 Percentage of participants

p-value: 0.7926295% CI: [-27.4, 11.9]Stratified Miettinen and Nurminen

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.