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CompletedNCT04776148Updated Feb 5, 2026Results posted

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)

A Phase 3 interventional study of pembrolizumab and lenvatinib in Colorectal Neoplasms, sponsored by Merck Sharp & Dohme LLC. Completed at 95 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-05.

Sponsored by Merck Sharp & Dohme LLC · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
563
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

The purpose of this study is to assess the safety and efficacy of lenvatinib (MK-7902/E7080) in combination with pembrolizumab (MK-3475) in participants with metastatic colorectal cancer. The study will also compare lenvatinib plus pembrolizumab with the standard of care treatment of regorafenib and TAS-102 (trifluridine and tipiracil hydrochloride).

The primary study hypothesis is that lenvatinib plus pembrolizumab is superior to standard of care with respect to overall survival.

Read the detailed description

The Global portion, or Global Cohort, will include all participants who are enrolled during the Global enrollment period and will be the primary analysis population for the study. After enrollment of the global portion of the study is complete, the study will remain open to enrollment in China alone until the target number of participants from China have been enrolled to meet local regulatory requirements.

The China Cohort will include both participants enrolled in China for the Global Cohort plus those participants enrolled in China as part of the China extension enrollment period.

Per the supplemental Statistical Analysis Plan (sSAP), China participants randomized after the enrollment of the global portion is closed as part of the China extension enrollment period will not be included in the global analysis populations.

As pre-specified in the protocol, safety and efficacy outcome measures for the China Cohort will be analyzed separately from the Global Cohort.

02

Conditions studied

  • Colorectal Neoplasms

Keywords

  • Programmed Cell Death Receptor 1 (PD-1)
  • Programmed Cell Death Receptor Ligand 1 (PD-L1)
  • Programmed Cell Death Receptor Ligand 2 (PD-L2)
  • PD-1
  • PDL1
  • PD-L1
  • PD-L2
03

In context

Colorectal Neoplasms

5,598 studies on the registry are indexed under Colorectal Neoplasms; 1,458 are open to participants now.

This study's enrollment of 563 is above the median of 77 across 4,122 interventional studies indexed under Colorectal Neoplasms.

Browse Colorectal Neoplasms studies →

Lead sponsor

Merck Sharp & Dohme LLC is the lead sponsor of 2,114 studies on the registry; 133 are open to participants now.

Of its 489 completed or terminated interventional studies of FDA-regulated products, 362 (74%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Has histologically or cytologically confirmed diagnosis of unresectable and metastatic colorectal adenocarcinoma (Stage IV A, B and C as defined by American Joint Committee on Cancer [AJCC] 8th edition). Note: Tumor must be determined to be NOT microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) by local testing

  • Has been previously treated for their disease and has shown disease progression as defined by RECIST 1.1 on or after or could not tolerate standard treatment, which must include ALL of the following agents if approved and locally available in the country where the participant is randomized:

    1. fluoropyrimidine, irinotecan and oxaliplatin
    2. with or without an anti-vascular endothelial growth factor (VEGF) monoclonal antibody (bevacizumab)
    3. with anti- epidermal growth factor receptor (EGFR) monoclonal antibodies (cetuximab or panitumumab) for RAS (KRAS/NRAS) wild-type (WT) participants
    4. BRAF inhibitor (in combination with cetuximab +/- binimetinib) for BRAF V600E mutated metastatic colon cancer (mCRC)
  • Has measurable disease per RECIST 1.1 assessed by the investigator
  • Has provided to a designated central laboratory an archival tumor tissue sample or newly obtained core, incisional, or excisional biopsy of a tumor lesion which has not been previously irradiated
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 3 days prior to randomization
  • Has a life expectancy of at least 3 months, based on the investigator assessment
  • Has the ability to swallow capsules or ingest a suspension orally or by a feeding tube
  • Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 millimeter of mercury (mmHg) with no change in antihypertensive medications within 1 week prior to randomization
  • Male participants must agree to the following during the treatment period and for at least 90 days after the last dose of regorafenib or TAS-102 and at least 7 days after the last dose of lenvatinib: refrain from donating sperm PLUS either be abstinent from heterosexual intercourse as their preferred and usual lifestyle or use contraception. The male contraception period should continue for at least 7 days after discontinuation of lenvatinib
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP) OR is a WOCBP and using a highly-effective contraceptive method during the treatment period and for at least 30 days after the last dose of lenvatinib, 120 days after the last dose of pembrolizumab, and 180 days after the last dose of regorafenib or TAS-102 (whichever is last) AND agrees not to donate eggs (ova, oocytes)
  • A WOCBP must have a negative highly sensitive pregnancy test (urine or serum) within 24 hours before the first dose of study treatment

Exclusion criteria

Exclusion Criteria:

  • Has a tumor that is microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) per local testing
  • Has presence of gastrointestinal condition, eg, malabsorption, that might affect the absorption of study drug.
  • Has present or progressive accumulation of pleural, ascitic, or pericardial fluid requiring drainage or diuretic drugs within 2 weeks prior to enrollment
  • Has radiographic evidence of encasement or invasion of a major blood vessel invasion or of intratumoral cavitation. In the chest, major blood vessels include the main pulmonary artery, the left and right pulmonary arteries, the 4 major pulmonary veins, the superior or inferior vena cava, and the aorta
  • Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study drug
  • Has clinically significant cardiovascular disease within 12 months from first dose of study intervention, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebral vascular accident, or cardiac arrhythmia associated with hemodynamic instability.

Participants with cardiac failure NYHA Class II, III and IV are not allowed to be assigned to the regorafenib in Arm B

  • Has a history of arterial thromboembolism within 12 months of start of study drug
  • Has urine protein ≥1 gram/24 hour
  • Has prolongation of QT interval corrected with Fridericia's formula (QTcF interval) to >480 milliseconds
  • Has left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition (MUGA) or echocardiogram (ECHO)
  • Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with certain exceptions
  • Has serious nonhealing wound, ulcer or bone fracture
  • Has had major surgery within 3 weeks prior to first dose of study treatment
  • Has received biologic response modifiers (eg, granulocyte colony-stimulating factor) within 4 weeks before study entry
  • Has preexisting ≥Grade 3 gastrointestinal or nongastrointestinal fistula
  • Has received prior treatment with a combination of an anti-PD-1, anti-PD-L1, or anti PD-L2 agent with anti-VEGF monoclonal antibodies or vascular endothelial growth factor receptor (VEGFR) inhibitors
  • Has previously received regorafenib or TAS-102
  • Has received prior systemic anti-cancer therapy including investigational agents within 28 days prior to randomization
  • Has received prior radiotherapy within 2 weeks of start of study treatment
  • Has received a live or live-attenuated vaccine within 30 days prior to the first dose of study treatment
  • Has known intolerance to lenvatinib, regorafenib, or TAS-102 and/or any of their excipients
  • Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days prior to the first dose of study treatment
  • Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
  • Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
  • Has an active autoimmune disease that has required systemic treatment in past 2 years
  • Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has an active infection requiring systemic therapy
  • Has a known history of Human Immunodeficiency Virus (HIV) infection
  • Has a known history of Hepatitis B or known active Hepatitis C virus infection
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study
  • Has had an allogenic tissue/solid organ transplant
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
563 participants (actual)

Study arms

  • Experimental
    lenvatinib+pembrolizumab

    Participants receive 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.

    Drug: pembrolizumab · Drug: lenvatinib

  • Active comparator
    standard of care treatment (regorafenib OR TAS-102)

    Participants receive 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.

    Drug: regorafenib · Drug: TAS-102 (trifluridine and tipiracil)

Interventions

  • Drugpembrolizumab

    IV infusion

    Also known as: KEYTRUDA®, MK-3475

  • Druglenvatinib

    oral capsule

    Also known as: MK-7902, E7080

  • Drugregorafenib

    oral tablet

    Also known as: STIVARGA®, REGONIX®

  • DrugTAS-102 (trifluridine and tipiracil)

    oral tablet

    Also known as: LONSURF®

06

What researchers measure

Primary outcomes

  1. Global Cohort: Overall Survival (OS)

    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.

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

  2. China Cohort: Overall Survival (OS)

    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.

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

Secondary outcomes

  1. 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)

    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.

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

  2. 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)

    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.

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

  3. Global Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

    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.

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

  4. China Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

    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.

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

  5. Global Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

    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.

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

  6. China Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

    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.

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

  7. Global Cohort: Number of Participants Who Experience an Adverse Event (AE)

    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.

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

  8. China Cohort: Number of Participants Who Experience an Adverse Event (AE)

    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.

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

  9. Global Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

    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.

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

  10. China Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

    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.

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

  11. 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

    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.

    Time frame: Baseline and 8 weeks

  12. Global Cohort: Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

    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.

    Time frame: Baseline and 8 weeks

  13. Global Cohort: Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score

    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.

    Time frame: Baseline and 8 weeks

  14. Global Cohort: Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

    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.

    Time frame: Baseline and 8 weeks

  15. 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

    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.

    Time frame: Up to approximately 21 months

  16. Global Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

    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.

    Time frame: Up to approximately 21 months

  17. Global Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score

    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.

    Time frame: Up to approximately 21 months

  18. Global Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

    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.

    Time frame: Up to approximately 21 months

07

Results

Posted Apr 9, 2024

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.

Participant flow — Overall Study
MilestoneLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Started282281
Treated279277
Global cohort efficacy241239
China cohort efficacy5347
Global cohort safety238235
China cohort safety5347
Completed00
Not completed282281
Withdrew: Death249260
Withdrew: Lost to follow-up01
Withdrew: Withdrawal by parent/guardian01
Withdrew: Withdrawal by subject34
Withdrew: Sponsor decision3015

Outcome measures

SecondaryGlobal 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)

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.

Time frame:
Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
Reported as:
Median · Months
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)
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
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)3.8 (3.7 to 5.1)3.3 (2.0 to 3.7)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Log Rank · p = 0.0003 (One-sided p-value based on log-rank test stratified by presence of liver metastasis) · Hazard ratio (hr): 0.69 · 95% CI 0.56 to 0.85
SecondaryChina 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)

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.

Time frame:
Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
Reported as:
Median · Months
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)
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
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)3.7 (2.9 to 3.9)2.4 (1.9 to 5.4)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Log Rank · p = 0.7421 (One-sided p-value based on log-rank test.) · Hazard ratio (hr): 1.15 · 85% CI 0.75 to 1.77
SecondaryGlobal Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

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.

Time frame:
Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
Reported as:
Number · Percentage of Participants
Global Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
Percentage of ParticipantsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR10.4 (6.8 to 14.9)1.7 (0.5 to 4.2)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Chi-squared · p = <0.0001 · Difference in percentage vs. soc: 8.7 · 95% CI 4.7 to 13.5Based on Miettinen \& Nurminen method stratified by presence of liver metastasis
SecondaryChina Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR

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.

Time frame:
Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
Reported as:
Number · Percentage of Participants
China Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
Percentage of ParticipantsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
China Cohort: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR7.5 (2.1 to 18.2)4.3 (0.5 to 14.5)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Chi-squared · p = 0.2456 · Difference in percentage vs. soc: 3.3 · 95% CI -7.7 to 14.3Based on Miettinen \& Nurminen method.
SecondaryGlobal Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

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.

Time frame:
Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
Reported as:
Median · Months
Global Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR11.1 (7.7 to NA)7.6 (6.0 to NA)
SecondaryChina Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR

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.

Time frame:
Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
Reported as:
Median · Months
China Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
China Cohort: Duration of Response (DOR) Per RECIST 1.1 as Assessed by BICR4.4 (3.5 to NA)NA (9.1 to NA)
SecondaryGlobal Cohort: Number of Participants Who Experience an Adverse Event (AE)

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.

Time frame:
Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
Reported as:
Count of participants · Participants
Global Cohort: Number of Participants Who Experience an Adverse Event (AE)
ParticipantsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Number of Participants Who Experience an Adverse Event (AE)237230
SecondaryChina Cohort: Number of Participants Who Experience an Adverse Event (AE)

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.

Time frame:
Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
Reported as:
Count of participants · Participants
China Cohort: Number of Participants Who Experience an Adverse Event (AE)
ParticipantsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
China Cohort: Number of Participants Who Experience an Adverse Event (AE)5347
SecondaryGlobal Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

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.

Time frame:
Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
Reported as:
Count of participants · Participants
Global Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
ParticipantsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)3710
SecondaryChina Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)

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.

Time frame:
Up to approximately 28 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
Reported as:
Count of participants · Participants
China Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)
ParticipantsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
China Cohort: Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE)85
SecondaryGlobal 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

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.

Time frame:
Baseline and 8 weeks
Reported as:
Least squares mean · Scores on a scale
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
Scores on a scaleLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
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-4.91 (-7.67 to -2.14)-7.62 (-10.48 to -4.76)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · cLDA model · p = 0.1553 (Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).) · Difference in least squares means: 2.71 · 95% CI -1.03 to 6.46
SecondaryGlobal Cohort: Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

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.

Time frame:
Baseline and 8 weeks
Reported as:
Least squares mean · Scores on a scale
Global Cohort: Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
Scores on a scaleLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score-6.16 (-8.51 to -3.82)-7.32 (-9.75 to -4.90)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · cLDA model · p = 0.4967 (Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).) · Difference in ls means: 1.16 · 95% CI -2.19 to 4.51
SecondaryGlobal Cohort: Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score

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.

Time frame:
Baseline and 8 weeks
Reported as:
Least squares mean · Scores on a scale
Global Cohort: Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score
Scores on a scaleLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Change From Baseline in EORTC QLQ-C30 Appetite Loss (Item 13) Score12.44 (8.50 to 16.38)9.08 (5.00 to 13.15)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · cLDA model · p = 0.2271 (Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).) · Difference in ls means: 3.36 · 95% CI -2.10 to 8.82
SecondaryGlobal Cohort: Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

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.

Time frame:
Baseline and 8 weeks
Reported as:
Least squares mean · Scores on a scale
Global Cohort: Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
Scores on a scaleLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Change From Baseline in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score-0.30 (-3.78 to 3.19)5.16 (1.56 to 8.77)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · cLDA model · p = 0.0264 (Based on a cLDA model with the PRO scores as the response variable with covariates for treatment by study visit interaction and stratification factor presence of liver metastasis (Yes/No).) · Difference in ls means: -5.46 · 95% CI -10.27 to -0.65
SecondaryGlobal 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

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.

Time frame:
Up to approximately 21 months
Reported as:
Median · Months
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
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
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 Score1.4 (1.1 to 1.9)1.4 (1.0 to 1.8)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Regression, Cox · p = 0.4338 · Hazard ratio (hr): 0.91 · 95% CI 0.73 to 1.14Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).
SecondaryGlobal Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score

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.

Time frame:
Up to approximately 21 months
Reported as:
Median · Months
Global Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: TTD in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score1.8 (1.4 to 2.0)2.0 (1.4 to 2.3)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Regression, Cox · p = 0.4316 (Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).) · Hazard ratio (hr): 1.10 · 95% CI 0.87 to 1.38
SecondaryGlobal Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score

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.

Time frame:
Up to approximately 21 months
Reported as:
Median · Months
Global Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: TTD in EORTC QLQ-C30 Appetite Loss (Item 13) Score1.4 (1.1 to 1.8)1.4 (1.1 to 1.9)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Regression, Cox · p = 0.5587 · Hazard ratio (hr): 1.06 · 95% CI 0.85 to 1.32Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).
SecondaryGlobal Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score

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.

Time frame:
Up to approximately 21 months
Reported as:
Median · Months
Global Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: TTD in EORTC Quality of Life Questionnaire-Colorectal Cancer-Specific 29 Items (QLQ-CR29) Bloating (Item 37) Score3.4 (2.3 to 5.2)3.2 (2.3 to 5.6)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Regression, Cox · p = 0.6794 (Two-sided p-value based on log-rank test stratified by presence of liver metastasis (Yes/No).) · Hazard ratio (hr): 0.95 · 95% CI 0.73 to 1.23
PrimaryGlobal Cohort: Overall Survival (OS)

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.

Time frame:
Up to approximately 22 months (through sSAP pre-specified Final Analysis database cut-off date of 20-Feb-2023)
Reported as:
Median · Months
Global Cohort: Overall Survival (OS)
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
Global Cohort: Overall Survival (OS)9.8 (8.4 to 11.6)9.3 (8.2 to 10.9)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Log Rank · p = 0.0379 · Hazard ratio (hr): 0.83 · 95% CI 0.68 to 1.02HR=Lenvatinib + pembrolizumab vs. SOC treatment
PrimaryChina Cohort: Overall Survival (OS)

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.

Time frame:
Up to approximately 35 months (through sSAP pre-specified Final Analysis database cut-off date of 27-Sep-2024)
Reported as:
Median · Months
China Cohort: Overall Survival (OS)
MonthsLenvatinib+PembrolizumabStandard of Care (SOC) Treatment
China Cohort: Overall Survival (OS)10.9 (8.8 to 16.5)10.2 (6.1 to 12.7)
Statistical analysis
  • Lenvatinib+Pembrolizumab vs Standard of Care (SOC) Treatment · Log Rank · p = 0.3574 · Hazard ratio (hr): 0.92 · 95% CI 0.60 to 1.42HR=Lenvatinib + pembrolizumab vs. SOC treatment

Adverse events

Collected over Up to approximately 41 months (through End of Trial database cut-off date of 27-Sep-2024). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Lenvatinib + Pembrolizumab251/282 (89%)117/279 (41.9%)273/279 (97.8%)
Standard Of Care Treatment264/281 (94%)66/277 (23.8%)263/277 (94.9%)
Most frequent serious events
Showing 10 of 166
Most frequent serious events
EventLenvatinib + PembrolizumabStandard Of Care Treatment
Abdominal painGastrointestinal disorders5/2796/277
Urinary tract infectionInfections and infestations6/2794/277
HypertensionVascular disorders6/2790/277
IleusGastrointestinal disorders5/2793/277
PneumoniaInfections and infestations5/2793/277
PyrexiaGeneral disorders4/2794/277
DiarrhoeaGastrointestinal disorders4/2793/277
Intestinal obstructionGastrointestinal disorders4/2791/277
COVID-19Infections and infestations4/2791/277
Acute kidney injuryRenal and urinary disorders4/2791/277
Most frequent other events
Showing 10 of 54
Most frequent other events
EventLenvatinib + PembrolizumabStandard Of Care Treatment
HypertensionVascular disorders156/27963/277
ProteinuriaRenal and urinary disorders136/27942/277
DiarrhoeaGastrointestinal disorders119/27964/277
HypothyroidismEndocrine disorders105/27919/277
NauseaGastrointestinal disorders66/27987/277
FatigueGeneral disorders78/27967/277
Decreased appetiteMetabolism and nutrition disorders75/27969/277
Aspartate aminotransferase increasedInvestigations67/27939/277
Weight decreasedInvestigations65/27926/277
AnaemiaBlood and lymphatic system disorders49/27960/277

Baseline characteristics

Baseline characteristics include data from 480 participants in the Global Cohort and 83 participants from the China extension (Total Study N=563)

Age, Continuous
Age, Continuous(Years)Lenvatinib+PembrolizumabStandard of Care (SOC) TreatmentTotal
Mean57.1 ± 11.757.2 ± 11.757.1 ± 11.7
Sex: Female, Male
Sex: Female, Male(Participants)Lenvatinib+PembrolizumabStandard of Care (SOC) TreatmentTotal
Female121116237
Male161165326
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Lenvatinib+PembrolizumabStandard of Care (SOC) TreatmentTotal
Hispanic or Latino261339
Not Hispanic or Latino255267522
Unknown or Not Reported112
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Lenvatinib+PembrolizumabStandard of Care (SOC) TreatmentTotal
American Indian or Alaska Native000
Asian122123245
Native Hawaiian or Other Pacific Islander000
Black or African American538
White152152304
More than one race112
Unknown or Not Reported224
Presence of Liver Metastasis
Presence of Liver Metastasis(Participants)Lenvatinib+PembrolizumabStandard of Care (SOC) TreatmentTotal
Yes192190382
No9091181
08

Study locations

95 sites
  • Pacific Cancer Care ( Site 0031)
    Monterey, California 93940, United States
  • Northwest Georgia Oncology Centers, a Service of Wellstar Cobb Hospital ( Site 0021)
    Marietta, Georgia 30060, United States
  • University of Chicago Medical Center-Medicine - Section of Hematology/Oncology - Gastrointestinal P
    Chicago, Illinois 60637, United States
  • MFSMC-HJWCI-Oncology Research ( Site 0012)
    Baltimore, Maryland 21237, United States
  • MedStar Good Samaritan Hospital-Oncology Research ( Site 0038)
    Baltimore, Maryland 21239, United States
  • Henry Ford Hospital ( Site 0024)
    Detroit, Michigan 48202, United States
  • St. Vincent Frontier Cancer Center ( Site 0005)
    Billings, Montana 59102, United States
  • Providence Portland Medical Center ( Site 0019)
    Portland, Oregon 97213, United States
  • Thomas Jefferson University - Clinical Trials Office ( Site 0027)
    Philadelphia, Pennsylvania 19107, United States
  • Inova Schar Cancer Institute ( Site 0022)
    Fairfax, Virginia 22031, United States
  • Blue Ridge Cancer Care ( Site 0036)
    Roanoke, Virginia 24014, United States
  • Northwest Medical Specialties, PLLC ( Site 0033)
    Tacoma, Washington 98405, United States
  • Hospital Británico de Buenos Aires-Oncology ( Site 0308)
    Ciudad Autónoma de Buenos Aires, Buenos Aires C1280AEB, Argentina
  • Fundación favaloro para la Docencia e Investigación Médica-Oncología ( Site 0301)
    Buenos Aires, Buenos Aires F.D. C1096AAS, Argentina
  • Instituto de Oncología de Rosario ( Site 0305)
    Rosario, Santa Fe Province S2000KZE, Argentina
  • Centro de Educación Médica e Investigaciones Clínicas (CEMIC)-Medical Oncology ( Site 0303)
    Buenos Aires, 1431, Argentina
  • IDIM - Instituto de Diagnóstico e Investigaciones Metabólicas ( Site 0300)
    Buenos Aires, C1012AAR, Argentina
  • Royal Brisbane and Women's Hospital-Medical Oncology Clinical Trials Unit, Cancer Care Services ( Si
    Brisbane, Queensland 4029, Australia
  • Gallipoli Medical Research Foundation-GMRF CTU ( Site 1500)
    Greenslopes, Queensland 4120, Australia
  • The Queen Elizabeth Hospital-Cancer Clinical Trials ( Site 1503)
    Woodville, South Australia 5011, Australia
  • Epworth Freemasons ( Site 1506)
    Melbourne, Victoria 3002, Australia
  • Western Health-Sunshine & Footscray Hospitals ( Site 1501)
    St Albans, Victoria 3021, Australia
  • Hollywood Private Hospital-Medical Oncology ( Site 1507)
    Perth, Western Australia 6009, Australia
  • Cross Cancer Institute-Department of Medical Oncology ( Site 0207)
    Edmonton, Alberta T6G 1Z2, Canada
  • NSHA-QEII Health Sciences Centre-Dickson Bldg-Dept. of Medical Oncology ( Site 0200)
    Halifax, Nova Scotia B3H 2Y9, Canada
  • Hamilton Health Sciences-Juravinski Cancer Centre ( Site 0205)
    Hamilton, Ontario L8V 4X2, Canada
  • North York General Hospital ( Site 0206)
    Toronto, Ontario M2K1E1, Canada
  • CIUSSS de l'Est-de-l'Île-de-Montréal ( Site 0211)
    Montreal, Quebec H1T 2M4, Canada
  • CHU de Quebec - Université Laval - Hotel Dieu de Quebec-Hemato-Dermato-Gyneco-Oncology ( Site 0203)
    Québec, Quebec G1R 3S1, Canada
  • The First People's Hospital of Foshan-Gastrointestinal oncology ( Site 1604)
    Foshan, Guangdong 528041, China
  • SUN YAT-SEN UNIVERSITY CANCER CENTRE ( Site 1600)
    Guangzhou, Guangdong 510060, China
  • Sir Run Run Shaw Hospital-Medical Oncology ( Site 1606)
    Hangzhou, Zhejiang 310016, China
  • Rigshospitalet ( Site 0702)
    Copenhagen, Capital Region 2100, Denmark
  • Herlev and Gentofte Hospital-Department of Oncology ( Site 0704)
    Copenhagen, Capital Region 2730, Denmark
  • Odense Universitetshospital ( Site 0700)
    Odense, Region Syddanmark 5000, Denmark
  • Vejle Sygehus-Department of Oncology ( Site 0701)
    Vejle, Region Syddanmark DK-7100, Denmark
  • Klinikum am Steinenberg-Kreiskliniken Reutlingen GmbH ( Site 0908)
    Reutlingen, Baden-Wurttemberg 72764, Germany
  • klinikum rechts der isar der technischen universität münchen-Klinik und Poliklinik für Innere Mediz
    Munich, Bavaria 81675, Germany
  • Onkodok GmbH ( Site 0907)
    Gütersloh, North Rhine-Westphalia 33332, Germany
  • Charité Universitaetsmedizin Berlin - Campus Mitte ( Site 0901)
    Berlin, 10117, Germany
  • Asklepios Altona-Oncology ( Site 0903)
    Hamburg, 22763, Germany
  • Rambam Health Care Campus-Oncology ( Site 0800)
    Haifa, 3109601, Israel
  • Shaare Zedek Medical Center-Oncology ( Site 0804)
    Jerusalem, 9013102, Israel
  • Hadassah Medical Center-Oncology ( Site 0802)
    Jerusalem, 9112001, Israel
  • Sheba Medical Center ( Site 0803)
    Ramat Gan, 5262100, Israel
  • Sourasky Medical Center-Oncology ( Site 0801)
    Tel Aviv, 6423906, Israel
  • Aichi Cancer Center Hospital ( Site 1701)
    Nagoya, Aichi-ken 4648681, Japan
  • National Cancer Center Hospital East ( Site 1700)
    Kashiwa, Chiba 277-8577, Japan
  • Kobe City Medical Center General Hospital ( Site 1707)
    Kobe, Hyōgo 650-0047, Japan
  • Kagawa University Hospital ( Site 1708)
    Kita, Kagawa-ken 761-0701, Japan
  • Kanagawa cancer center ( Site 1705)
    Yokohama, Kanagawa 2418515, Japan
  • Kindai University Hospital- Osakasayama Campus-Medical Oncology ( Site 1704)
    Sayama, Osaka 589-8511, Japan
  • Saitama Prefectural Cancer Center ( Site 1703)
    Ina-machi, Saitama 362-0806, Japan
  • Shizuoka Cancer Center ( Site 1706)
    Nakatogari, Shizuoka 411-8777, Japan
  • National Hospital Organization Kyushu Cancer Center ( Site 1709)
    Fukuoka, 811-1395, Japan
  • National Cancer Center Hospital ( Site 1702)
    Tokyo, 104-0045, Japan
  • Japanese Foundation for Cancer Research-GI Oncology ( Site 1710)
    Tokyo, 135-8550, Japan
  • GBUZ Republican Clinical Oncological Dispensary-Antitumor drug therapy department ( Site 1109)
    Ufa, Baskortostan, Respublika 450054, Russia
  • Saint-Petersburg City Clinical Oncology Dispensary-Department of chemotherapy ( Site 1100)
    Saint Petersburg, Leningradskaya Oblast' 198255, Russia
  • The National Medico-Surgical Center N.I. Pirogov ( Site 1102)
    Moscow, Moscow 105203, Russia
  • Fed State Budgetary Inst N.N. Blokhin Med Center of Oncology MHRF ( Site 1107)
    Moscow, Moscow 115478, Russia
  • First Moscow State Medical University I.M. Sechenov-Interhospital Institution ""Health Management (
    Moscow, Moscow 119991, Russia
  • SVERDLOVSK REGIONAL ONCOLOGY DISPENSARY ( Site 1108)
    Yekaterinburg, Sverdlovsk Oblast 620905, Russia
  • SHBI Leningrad Regional Clinical Oncology Dispensary-Clinical Trials Department ( Site 1111)
    Saint Petersburg, 188663, Russia
  • Korea University Anam Hospital ( Site 1806)
    Seoul, 02841, South Korea
  • Seoul National University Hospital-Internal Medicine ( Site 1800)
    Seoul, 03080, South Korea
  • Severance Hospital, Yonsei University Health System-Medical oncology ( Site 1801)
    Seoul, 03722, South Korea
  • Asan Medical Center ( Site 1803)
    Seoul, 05505, South Korea
  • Samsung Medical Center-Division of Hematology/Oncology ( Site 1804)
    Seoul, 06351, South Korea
  • The Catholic Univ. of Korea Seoul St. Mary's Hospital ( Site 1802)
    Seoul, 06591, South Korea
  • Hospital Universitario Marqués de Valdecilla ( Site 1201)
    Santander, Cantabria 39008, Spain
  • Hospital Universitario Central de Asturias-Digestive ( Site 1200)
    Oviedo, Principality of Asturias 33011, Spain
  • Hospital Universitari Vall d'Hebron-Oncology ( Site 1204)
    Barcelona, 08035, Spain
  • HOSPITAL GENERAL UNIVERSITARIO GREGORIO MARAÑON ( Site 1205)
    Madrid, 28007, Spain
  • Hospital Universitario Virgen de Valme-Departamento de Oncologia ( Site 1207)
    Seville, 41014, Spain
  • China Medical University Hospital-Surgical Department ( Site 1903)
    Taichung, 40447, Taiwan
  • NATIONAL CHENG-KUNG UNI. HOSP. ( Site 1904)
    Tainan, 704, Taiwan
  • National Taiwan University Hospital ( Site 1900)
    Taipei, 10002, Taiwan
  • Taipei Veterans General Hospital-Oncology ( Site 1901)
    Taipei, 11217, Taiwan
  • Chang Gung Medical Foundation.Linkou Branch ( Site 1902)
    Taoyuan, 333, Taiwan
  • Hacettepe Universitesi-oncology hospital ( Site 1302)
    Ankara, 06230, Turkey (Türkiye)
  • Memorial Ankara Hastanesi-Medical Oncology ( Site 1304)
    Ankara, 06520, Turkey (Türkiye)
  • Trakya University-Oncology ( Site 1303)
    Edirne, 22030, Turkey (Türkiye)
  • Acıbadem Maslak Hastanesi ( Site 1307)
    Istanbul, 34457, Turkey (Türkiye)
  • Istanbul Universitesi Cerrahpasa-Medical Oncology ( Site 1300)
    Istanbul, 34668, Turkey (Türkiye)
  • TC Saglik Bakanligi Goztepe Prof. Dr. Suleyman Yalcin Sehir Hastanesi-oncology ( Site 1301)
    Istanbul, 34722, Turkey (Türkiye)
  • Ege University Medicine of Faculty-Medical Oncology ( Site 1305)
    Izmir, 35100, Turkey (Türkiye)
  • İnönü Üniversitesi Turgut Özal Tıp Merkezi ( Site 1306)
    Malatya, 44280, Turkey (Türkiye)
  • Addenbrooke's Hospital ( Site 1407)
    Cambridge, Cambridgeshire CB2 0QQ, United Kingdom
  • UCLH-Cancer Clinical Trials Unit ( Site 1400)
    London, Essex NW1 2PG, United Kingdom
  • Guy's & St Thomas' NHS Foundation Trust ( Site 1404)
    London, London, City of SE1 9RT, United Kingdom
  • ROYAL MARSDEN HOSPITAL (CHELSEA) ( Site 1403)
    London, London, City of SW3 6JJ, United Kingdom
  • Western General Hospital ( Site 1401)
    Edinburgh, Midlothian EH4 2XU, United Kingdom
  • Royal Marsden Hospital (Sutton) ( Site 1409)
    London, Surrey SM3 5PT, United Kingdom
  • The Christie-Medical Oncology ( Site 1411)
    Manchester, M20 4BX, United Kingdom
09

References and documents

Publications

  • Kawazoe A, Xu RH, Garcia-Alfonso P, Passhak M, Teng HW, Shergill A, Gumus M, Qvortrup C, Stintzing S, Towns K, Kim TW, Shiu KK, Cundom J, Ananda S, Lebedinets A, Fu R, Jain R, Adelberg D, Heinemann V, Yoshino T, Elez E; LEAP-017 Investigators. Lenvatinib Plus Pembrolizumab Versus Standard of Care for Previously Treated Metastatic Colorectal Cancer: Final Analysis of the Randomized, Open-Label, Phase III LEAP-017 Study. J Clin Oncol. 2024 Aug 20;42(24):2918-2927. doi: 10.1200/JCO.23.02736. Epub 2024 Jun 4. PubMed 38833658 ↗

Study documents

  • Study protocol · Jul 14, 2022
  • Statistical analysis plan · Jun 24, 2025

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 5, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04776148
Lead sponsor
Merck Sharp & Dohme LLC
Collaborators
Eisai Inc.
Responsible party
Sponsor
First posted
Mar 1, 2021
Start date
Mar 29, 2021
Primary completion
Sep 27, 2024
Completion
Sep 27, 2024
Results posted
Apr 9, 2024
Last update
Feb 5, 2026

Study contacts

Medical Director
study director · Merck Sharp & Dohme LLC

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.

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Discussion

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