Trial Outcomes & Findings for 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) (NCT NCT03829332)

Last Updated: 2025-04-16

Results Overview

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. The appearance of one or more new lesions was also considered PD. Data are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 was presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

623 participants

Primary outcome timeframe

Up to approximately 25 months

Results posted on

2025-04-16

Participant Flow

Of the 623 total participants randomized in the MK-7902-007 global study, 80 were also randomized in the China extension study for MK-7902-007 (NCT04676412).

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	309	314
Overall Study Treated	309	312
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	309	314

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Sponsor Decision	71	72
Overall Study Death	225	230
Overall Study Lost to Follow-up	1	3
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	11	9

Baseline Characteristics

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)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=314 Participants 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.	Total n=623 Participants Total of all reporting groups
Age, Continuous	64.6 years STANDARD_DEVIATION 9.6 • n=5 Participants	65.4 years STANDARD_DEVIATION 8.8 • n=7 Participants	65.0 years STANDARD_DEVIATION 9.2 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	90 Participants n=7 Participants	169 Participants n=5 Participants
Sex: Female, Male Male	230 Participants n=5 Participants	224 Participants n=7 Participants	454 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	32 Participants n=5 Participants	30 Participants n=7 Participants	62 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	266 Participants n=5 Participants	269 Participants n=7 Participants	535 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants	3 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) Asian	103 Participants n=5 Participants	104 Participants n=7 Participants	207 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	188 Participants n=5 Participants	193 Participants n=7 Participants	381 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 0	110 Participants n=5 Participants	108 Participants n=7 Participants	218 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status ECOG = 1	199 Participants n=5 Participants	206 Participants n=7 Participants	405 Participants n=5 Participants
Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline TPS = 1-49%	172 Participants n=5 Participants	175 Participants n=7 Participants	347 Participants n=5 Participants
Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline TPS = ≥ 50%	137 Participants n=5 Participants	139 Participants n=7 Participants	276 Participants n=5 Participants
Geographic Region East Asia	103 Participants n=5 Participants	104 Participants n=7 Participants	207 Participants n=5 Participants
Geographic Region Non-East Asia	206 Participants n=5 Participants	210 Participants n=7 Participants	416 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to approximately 25 months

Population: The analysis population consisted of all randomized participants.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=314 Participants 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.
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	6.6 Months Interval 6.1 to 8.2	4.2 Months Interval 4.1 to 6.2

PRIMARY outcome

Timeframe: Up to approximately 25 months

Population: The analysis population consisted of all randomized participants.

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

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=314 Participants 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.
Overall Survival (OS)	14.1 Months Interval 11.4 to 19.0	16.4 Months Interval 12.6 to 20.6

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: The analysis population consisted of all randomized participants.

ORR was defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR as assessed by BICR per RECIST 1.1 is presented.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=314 Participants 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.
Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	40.5 Percentage of Participants Interval 34.9 to 46.2	27.7 Percentage of Participants Interval 22.8 to 33.0

SECONDARY outcome

Timeframe: Through 90 days post last dose of study treatment (Up to approximately 27 months)

Population: All randomized participants who received at least one dose of study treatment.

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

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=312 Participants 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.
Number of Participants Who Experienced an Adverse Event (AE)	306 Participants	294 Participants

SECONDARY outcome

Timeframe: Through last dose of study treatment (Up to approximately 24 months)

Population: All randomized participants who received at least one dose of study treatment.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=312 Participants 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.
Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)	98 Participants	41 Participants

SECONDARY outcome

Timeframe: Baseline and Week 21

Population: All randomized participants who have received at least one dose of the study intervention and had at least one EORTC QLQ-C30 assessment data available for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=308 Participants 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.
Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score	-1.48 Score on a scale Interval -4.09 to 1.13	2.42 Score on a scale Interval -0.24 to 5.08

SECONDARY outcome

Timeframe: Baseline and Week 21

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-C30 Item 31 assessment data available.

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. A lower score indicates a better outcome. Per protocol, the change from baseline in cough (EORTC QLQ-LC13 Item 31) score was presented.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=307 Participants 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.
Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score	-9.53 Score on a scale Interval -12.94 to -6.13	-5.04 Score on a scale Interval -8.51 to -1.57

SECONDARY outcome

Timeframe: Baseline and Week 21

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-C30 Item 40 assessment data available.

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. A lower score indicates a better outcome. Per protocol, the change from baseline in EORTC QLQ-LC13 chest pain (Item 40) score was presented.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=307 Participants 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.
Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score	-4.64 Score on a scale Interval -7.45 to -1.84	-3.55 Score on a scale Interval -6.42 to -0.68

SECONDARY outcome

Timeframe: Baseline and Week 21

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-C30 Item 8 assessment data available.

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. Per protocol, the change from baseline in EORTC QLQ-C30 dyspnea (Item 8) score was presented.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=308 Participants 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.
Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	-1.35 Score on a scale Interval -4.75 to 2.04	-0.47 Score on a scale Interval -3.94 to 3.0

SECONDARY outcome

Timeframe: Baseline and Week 21

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-C30 Items 1-5 assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=309 Participants 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.	Pembrolizumab + Placebo n=308 Participants 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.
Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	-6.73 Score on a scale Interval -9.35 to -4.1	-3.72 Score on a scale Interval -6.4 to -1.04

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-C30 Item 29 and Item 30 assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=304 Participants 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.	Pembrolizumab + Placebo n=297 Participants 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.
Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status /Quality of Life (Items 29 & 30) Scale Combined Score	NA Months Interval 14.1 to NA = Median and upper limit of 95%CI was not reached due to insufficient number of participants with an event.	NA Months Interval 19.3 to NA = Median and upper limit of 95%CI was not reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-LC13 Item assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=304 Participants 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.	Pembrolizumab + Placebo n=294 Participants 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.
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score	NA Months NA = Median, lower and upper limit of 95%CI was not reached due to insufficient number of participants with an event.	NA Months NA = Median, lower and upper limit of 95%CI was not reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-LC13 Item 40 assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=304 Participants 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.	Pembrolizumab + Placebo n=294 Participants 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.
Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score	NA Months NA = Median, lower and upper limit of 95%CI were not reached due to insufficient number of participants with an event.	NA Months NA = Median, lower and upper limit of 95%CI were not reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ Item 8 assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=304 Participants 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.	Pembrolizumab + Placebo n=297 Participants 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.
Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score	NA Months NA = Median, lower and upper limit of 95%CI were not reached due to insufficient number of participants with an event.	NA Months Interval 20.8 to NA = Median and upper limit of 95%CI were not reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All randomized participants who received at least one dose of study treatment and have at least one EORTC-QLQ-C30 Items 1-5 assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=304 Participants 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.	Pembrolizumab + Placebo n=297 Participants 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.
Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	18.8 Months Interval 14.1 to NA = Upper limit of 95%CI could not be reached due to insufficient number of participants with an event.	NA Months Interval 20.0 to NA = Median and upper limit of 95%CI could not be reached due to insufficient number of participants with an event.

SECONDARY outcome

Timeframe: Up to approximately 25 months

Population: All randomized participants who received at least one dose of study treatment and have at least one had at least one EORTC-QLQ-C30 or EORTC QLQ-LC13 assessment data available.

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.

Outcome measures

Outcome measures
Measure	Pembrolizumab + Lenvatinib n=49 Participants 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.	Pembrolizumab + Placebo n=55 Participants 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.
Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)	5.78 Months Interval 2.79 to NA = Upper limit of 95%CI could not be reached due to insufficient number of participants with an event.	NA Months Interval 3.45 to NA = Median and upper limit of 95%CI could not be reached due to insufficient number of participants with an event.

Adverse Events

Lenvatinib + Pembrolizumab

Serious events: 192 serious events

Other events: 296 other events

Deaths: 229 deaths

Placebo + Pembrolizumab

Serious events: 118 serious events

Other events: 275 other events

Deaths: 232 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme LLC

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor will generally support publication of multicenter studies only in their entirety and not as individual site data. In this case, a coordinating investigator will be designated by mutual agreement. If publication activity is not directed by the Sponsor, the investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. This allows the Sponsor to protect proprietary information and to provide comments.
Publication restrictions are in place

Restriction type: OTHER