Trial Outcomes & Findings for Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017) (NCT NCT04776148)

Last Updated: 2026-02-05

Results Overview

OS was defined as the time from randomization to the date of death from any cause. Per the supplemental Statistical Analysis Plan (sSAP), Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

563 participants

Primary outcome timeframe

Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Results posted on

2026-02-05

Participant Flow

A total of 480 participants were enrolled in the Global Cohort, including 17 participants from China. An additional 83 participants were subsequently enrolled in the China extension, bringing the total number of participants in the China Cohort to 100 and the overall study population to 563. These results have been updated to include data from the China Cohort.

Primary Completion for the study is being updated to 27-Sep-2024 to reflect that the protocol specified non-alpha controlled final analyses for the China Cohort was conducted with a 27-Sep 2024 data cutoff, after the protocol-specified final analyses of the Global Cohort was completed on 20-Feb-2023. Final Analysis of all outcome measures for the Global Cohort was conducted with a data cut-off of 20-Feb-2023.

Participant milestones

Participant milestones
Measure	Lenvatinib+Pembrolizumab Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.	Standard of Care (SOC) Treatment Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.
Overall Study STARTED	282	281
Overall Study Treated	279	277
Overall Study Global Cohort Efficacy	241	239
Overall Study China Cohort Efficacy	53	47
Overall Study Global Cohort Safety	238	235
Overall Study China Cohort Safety	53	47
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	282	281

Reasons for withdrawal

Reasons for withdrawal
Measure	Lenvatinib+Pembrolizumab Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.	Standard of Care (SOC) Treatment Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.
Overall Study Death	249	260
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Parent/Guardian	0	1
Overall Study Withdrawal by Subject	3	4
Overall Study Sponsor Decision	30	15

Baseline Characteristics

Study of Lenvatinib (MK-7902/E7080) in Combination With Pembrolizumab (MK-3475) Versus Standard of Care in Participants With Metastatic Colorectal Cancer (MK-7902-017/E7080-G000-325/LEAP-017)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Lenvatinib+Pembrolizumab n=282 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.	Standard of Care (SOC) Treatment n=281 Participants Participants received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Total n=563 Participants Total of all reporting groups
Age, Continuous	57.1 Years STANDARD_DEVIATION 11.7 • n=25 Participants	57.2 Years STANDARD_DEVIATION 11.7 • n=26 Participants	57.1 Years STANDARD_DEVIATION 11.7 • n=51 Participants
Sex: Female, Male Female	121 Participants n=25 Participants	116 Participants n=26 Participants	237 Participants n=51 Participants
Sex: Female, Male Male	161 Participants n=25 Participants	165 Participants n=26 Participants	326 Participants n=51 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=25 Participants	13 Participants n=26 Participants	39 Participants n=51 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	255 Participants n=25 Participants	267 Participants n=26 Participants	522 Participants n=51 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=25 Participants	1 Participants n=26 Participants	2 Participants n=51 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants
Race (NIH/OMB) Asian	122 Participants n=25 Participants	123 Participants n=26 Participants	245 Participants n=51 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants	0 Participants n=26 Participants	0 Participants n=51 Participants
Race (NIH/OMB) Black or African American	5 Participants n=25 Participants	3 Participants n=26 Participants	8 Participants n=51 Participants
Race (NIH/OMB) White	152 Participants n=25 Participants	152 Participants n=26 Participants	304 Participants n=51 Participants
Race (NIH/OMB) More than one race	1 Participants n=25 Participants	1 Participants n=26 Participants	2 Participants n=51 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=25 Participants	2 Participants n=26 Participants	4 Participants n=51 Participants
Presence of Liver Metastasis Yes	192 Participants n=25 Participants	190 Participants n=26 Participants	382 Participants n=51 Participants
Presence of Liver Metastasis No	90 Participants n=25 Participants	91 Participants n=26 Participants	181 Participants n=51 Participants

PRIMARY outcome

Timeframe: Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Population: All randomized participants in the Global Cohort included in the treatment arm to which they were randomized.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=239 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=241 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Overall Survival (OS)	9.3 Months Interval 8.2 to 10.9	9.8 Months Interval 8.4 to 11.6

PRIMARY outcome

Timeframe: Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

Population: All randomized participants in the China Cohort (17 participants enrolled in the Global Cohort and 83 participants enrolled in the China extension) included in the treatment arm to which they were randomized.

OS was defined as the time from randomization to the date of death from any cause. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=47 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=53 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
China Cohort: Overall Survival (OS)	10.2 Months Interval 6.1 to 12.7	10.9 Months Interval 8.8 to 16.5

SECONDARY outcome

Timeframe: Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Population: All randomized participants in the Global Cohort included in the treatment arm to which they were randomized.

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 occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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. PFS as assessed by BICR per modified RECIST 1.1 is presented. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=239 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=241 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: 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)	3.3 Months Interval 2.0 to 3.7	3.8 Months Interval 3.7 to 5.1

SECONDARY outcome

Timeframe: Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

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 occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, 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. PFS as assessed by BICR per modified RECIST 1.1 is presented. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=47 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=53 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
China Cohort: 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)	2.4 Months Interval 1.9 to 5.4	3.7 Months Interval 2.9 to 3.9

SECONDARY outcome

Timeframe: Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Population: All randomized participants in the Global Cohort included in the treatment arm to which they were randomized.

ORR is 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, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR per modified RECIST 1.1 assessed by BICR is presented. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=239 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=241 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	1.7 Percentage of Participants Interval 0.5 to 4.2	10.4 Percentage of Participants Interval 6.8 to 14.9

SECONDARY outcome

Timeframe: Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

ORR is 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, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ. ORR per modified RECIST 1.1 assessed by BICR is presented. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=47 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=53 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
China Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	4.3 Percentage of Participants Interval 0.5 to 14.5	7.5 Percentage of Participants Interval 2.1 to 18.2

SECONDARY outcome

Timeframe: Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Population: Randomized participants in the Global Cohort who had a confirmed complete or partial response, included in the treatment group to which they were randomized.

For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is 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 is also considered PD. DOR as assessed by BICR per modified RECIST 1.1 is presented. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=4 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=25 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	7.6 Months Interval 6.0 to NA=Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse	11.1 Months Interval 7.7 to NA=Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

Population: Randomized participants in the China Cohort (17 participants enrolled in the Global Cohort and 83 participants enrolled in the China extension) who had a confirmed complete or partial response, included in the treatment arm to which they were randomized.

For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the time from the first documented evidence of CR or PR until PD or death from any cause, whichever occurs first. Per RECIST 1.1 modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, or death from any cause, PD is 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 is also considered PD. DOR as assessed by BICR per modified RECIST 1.1 is presented. Per the sSAP, the China Cohort was evaluated for efficacy separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=2 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=4 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
China Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR	NA Months Interval 9.1 to NA=Median duration and upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse	4.4 Months Interval 3.5 to NA=Upper limit not reached at time of data cut-off due to insufficient number of responding participants with relapse

SECONDARY outcome

Timeframe: Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

Population: All randomized participants in the Global Cohort who received at least one dose of study treatment. Two participants randomized to pembrolizumab plus lenvatinib group were incorrectly treated with SOC; these participants were included in the SOC group for safety analyses.

An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=235 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=238 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Number of Participants Who Experience an Adverse Event (AE)	230 Participants	237 Participants

SECONDARY outcome

Timeframe: Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

Population: All randomized participants in the China Cohort (17 participants enrolled in the Global Cohort and 83 participants enrolled in the China extension) who received at least one dose of study treatment.

An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Per the sSAP, the China Cohort was evaluated for safety separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=47 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=53 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
China Cohort: Number of Participants Who Experience an Adverse Event (AE)	47 Participants	53 Participants

SECONDARY outcome

Timeframe: Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)

An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued any study treatment due to an adverse event is presented. Per the sSAP, Final Analysis for the Global Cohort was performed with a data cut-off date of 20-Feb-2023.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=235 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=238 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	10 Participants	37 Participants

SECONDARY outcome

Timeframe: Up to approximately 28 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)

An adverse event is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinued any study treatment due to an adverse event is presented. Per the sSAP, the China Cohort was evaluated for safety separately from the Global Cohort, with Final Analysis performed using a data cut-off of 27-Sep-2024.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=47 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=53 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
China Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)	5 Participants	8 Participants

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this Patient Reported Outcome (PRO) was not pre-specified for the China Cohort and was thus not analyzed.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (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). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented. A higher score indicates a better outcome.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=229 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=234 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Change From Baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	-7.62 Scores on a scale Interval -10.48 to -4.76	-4.91 Scores on a scale Interval -7.67 to -2.14

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) 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. Higher scores meant a better level of function. The change from baseline in the EORTC QLQ-C30 Physical Functioning (Items 1-5) scale score is presented.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=229 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=234 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	-7.32 Scores on a scale Interval -9.75 to -4.9	-6.16 Scores on a scale Interval -8.51 to -3.82

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 appetite loss and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire, including a single-item scale score for appetite loss (QLQ-C30 Item 13). For this item, individual responses to the question "Have you lacked appetite?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-C30 appetite loss (Item 13) scale score is presented.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=230 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=234 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score	9.08 Scores on a scale Interval 5.0 to 13.15	12.44 Scores on a scale Interval 8.5 to 16.38

SECONDARY outcome

Timeframe: Baseline and 8 weeks

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-CR29 and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

The EORTC QLQ-CR29 is a health-related quality-of life (QoL) questionnaire specific for colorectal cancer, including a single-item scale score for bloating (QLQ-CR29 Item 37). For this item, individual responses to the question "Did you have a bloated feeling in your abdomen?" are given on a 4-point scale (1=Not at all; 4=Very much). Scores are transformed to a range from 0-100, with a lower score indicating a better outcome. The change from baseline in the EORTC QLQ-CR29 bloating (Item 37) scale score is presented.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=230 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=234 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score	5.16 Scores on a scale Interval 1.56 to 8.77	-0.30 Scores on a scale Interval -3.78 to 3.19

SECONDARY outcome

Timeframe: Up to approximately 21 months

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 GHS/QoL TTD and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in Global Health Status (GHS; EORTC QLQ-C30 Item 29) \& Quality of Life (QoL; EORTC QLQ-C30 Item 30) combined score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in GHS and QoL combined score, is presented. A longer TTD indicates a better outcome.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=220 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=227 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: Time to Deterioration (TTD) in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Global Health Status (Item 29) and Quality of Life (Item 30) Combined Score	1.4 Months Interval 1.0 to 1.8	1.4 Months Interval 1.1 to 1.9

SECONDARY outcome

Timeframe: Up to approximately 21 months

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 Physical Functioning TTD and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score, is presented. A longer TTD indicates a better outcome.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=221 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=226 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	2.0 Months Interval 1.4 to 2.3	1.8 Months Interval 1.4 to 2.0

SECONDARY outcome

Timeframe: Up to approximately 21 months

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-C30 Appetite Loss TTD and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (increase) from baseline in appetite loss (QLQ-C30 Item 13) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point change (increase) from baseline in appetite loss score, is presented. A longer TTD indicates a better outcome.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=221 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=226 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score	1.4 Months Interval 1.1 to 1.9	1.4 Months Interval 1.1 to 1.8

SECONDARY outcome

Timeframe: Up to approximately 21 months

Population: All participants in the Global Cohort who have at least one assessment available for EORTC QLQ-CR29 Bloating TTD and have received at least one dose of the study intervention. Per the sSAP, this PRO was not pre-specified for the China Cohort and was thus not analyzed.

TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (increase) from baseline in bloating (QLQ-CR29 Item 37) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point change (increase) from baseline in bloating score, is presented. A longer TTD indicates a better outcome.

Outcome measures

Outcome measures
Measure	Standard of Care (SOC) Treatment n=221 Participants Participants enrolled in China received regorafenib 160 mg via oral tablet once daily on Days 1 through 21 of each 4-week cycle OR TAS-102 (trifluridine and tipiracil hydrochloride) 35 mg/m\^2 via oral tablet twice a day on Days 1 through 5 and Days 8-12 of each 4-week cycle until progressive disease.	Lenvatinib+Pembrolizumab n=224 Participants Participants received pembrolizumab 400 mg via intravenous (IV) infusion on Day 1 of each 6-week (Q6W) Cycle for up to 18 cycles (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily until progressive disease.
Global Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score	3.2 Months Interval 2.3 to 5.6	3.4 Months Interval 2.3 to 5.2

Adverse Events

Lenvatinib + Pembrolizumab

Serious events: 117 serious events

Other events: 273 other events

Deaths: 251 deaths

Standard Of Care Treatment

Serious events: 66 serious events

Other events: 263 other events

Deaths: 264 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 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