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CompletedNCT03829319Updated Feb 5, 2026Results posted

Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006)

A Phase 3 interventional study of Pembrolizumab and Carboplatin in Nonsquamous Non-small Cell Lung Cancer, sponsored by Merck Sharp & Dohme LLC. Completed at 158 sites in 17 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
761
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 pemetrexed + platinum chemotherapy + pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults with metastatic nonsquamous non-small cell lung cancer.

The primary study hypotheses state that: 1) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST 1.1) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab, and 2) the combination of lenvatinib + platinum doublet chemotherapy + pembrolizumab prolongs Overall Survival (OS) compared to matching placebo + platinum doublet chemotherapy + pembrolizumab.

02

Conditions studied

  • Nonsquamous Non-small Cell Lung Cancer

Keywords

  • programmed cell death 1 (PD-1, PD1)
  • programmed cell death-ligand 1 (PD-L1, PDL1)
  • programmed cell death-ligand 2 (PD-L2, PDL2)
03

In context

Parkinson Disease 4, Autosomal Dominant Lewy Body

152 studies on the registry are indexed under Parkinson Disease 4, Autosomal Dominant Lewy Body; 34 are open to participants now.

This study's enrollment of 761 is above the median of 302 across 141 interventional studies indexed under Parkinson Disease 4, Autosomal Dominant Lewy Body.

Browse Parkinson Disease 4, Autosomal Dominant Lewy Body 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

  • Histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer [AJCC], version 8 or current version), nonsquamous NSCLC.
  • Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated as primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat Sarcoma (KRAS) gene mutation).
  • Have measurable disease based on RECIST 1.1. Note: Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
  • Provided an archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (not previously irradiated).
  • Life expectancy of at least 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization.
  • Contraceptive use by men should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed.

  • Male participants must agree for at least 7 days after the last dose of lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents to:

    1. Refrain from donating sperm PLUS either:
    2. Be abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR

    3. Must agree to use contraception unless confirmed to be azoopsermic (vasectomized or secondary to medical cause) as detailed below:

      1. Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.

Note: 7 days after lenvatinib/matching placebo is stopped, if the participant is on pembrolizumab only and is greater than 180 days post chemotherapy, no male contraception measures are needed.

  • Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

  • Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies:

    1. Is not a WOCBP OR
    2. Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days post pembrolizumab and/or 30 days post-lenvatinib/matching placebo, and up to 180 days post last dose of chemotherapeutic agents, whichever occurs last.
  • Adequate organ function.
  • Adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week prior to randomization. Note: Participants must not have a history of uncontrolled or poorly-controlled hypertension, defined as >150/90 mm Hg for >4 weeks despite standard medical management.

Exclusion criteria

Exclusion Criteria:

  • Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
  • History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
  • Radiographic evidence of intratumoral caviations, encasement, or invasion of a major blood vessel. Additionally, the degree of proximity to major blood vessels should be considered for exclusion because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis after lenvatinib-therapy. (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).
  • Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. Note: The time requirement also does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.
  • Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
  • Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
  • Has had allogeneic tissue/solid organ transplant.
  • Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
  • Known history of Hepatitis B or active Hepatitis C. No testing for Hepatitis B or Hepatitis C is required unless mandated by the local health authority.
  • History of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
  • Active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.
  • Significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
  • Known history of active tuberculosis.
  • Active infection requiring systemic therapy.
  • Has not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention.
  • Previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity to any component of lenvatinib or pembrolizumab, or as applicable, carboplatin, cisplatin, or pemetrexed.
  • A WOCBP who has a positive urine pregnancy test within 24 hours prior to randomization or treatment allocation. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
  • Received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed as long as therapy was completed at least 6 months prior to the diagnosis of metastatic NSCLC.
  • Received prior treatment with pembrolizumab or any other anti-programmed cell death (PD)-1, anti-PD-L1, anti-PD-L2 agent, with lenvatinib or any other receptor tyrosine kinase inhibitor (RTKi), or with an agent directed to another stimulatory or co-inhibitory T cell receptor.
  • Received radiotherapy within 14 days prior to the first dose of study intervention or received lung radiation therapy of >30 Gy within 6 months prior to the first dose of study intervention. Note: Participants must have recovered from all radiation-related toxicities to Grade ≤1, not required corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
  • Received systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) within 7 days prior to the first dose of study intervention.
  • Received a live or live attenuated vaccine within 30 days prior to the first dose of study intervention. Note: killed vaccines are allowed.
  • Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks prior to the first dose of study intervention.
  • Has a prolongation of QTc interval (calculated using Fridericia's formula) of >480 msecl.
  • Left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
  • Has preexisting ≥Grade 3 gastrointestinal or non-gastrointestinal fistula
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
761 participants (actual)

Study arms

  • Experimental
    Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib

    Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.

    Biological: Pembrolizumab · Drug: Carboplatin · Drug: Cisplatin · Drug: Pemetrexed · Drug: Lenvatinib

  • Placebo comparator
    Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

    In Parts 1 and 2: Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.

    Biological: Pembrolizumab · Drug: Carboplatin · Drug: Cisplatin · Drug: Pemetrexed · Drug: Placebo matching lenvatinib

Interventions

  • BiologicalPembrolizumab

    IV infusion Q3W

    Also known as: MK-3475

  • DrugCarboplatin

    IV infusion Q3W

  • DrugCisplatin

    IV infusion Q3W

  • DrugPemetrexed

    IV infusion Q3W

  • DrugLenvatinib

    Oral capsule once daily

    Also known as: MK-7902, E7080

  • DrugPlacebo matching lenvatinib

    Oral capsule once daily

06

What researchers measure

Primary outcomes

  1. Part 1: Number of Participants With a Dose-limiting Toxicity (DLT)

    Dose-limiting toxicity using Common Terminology Criteria for Adverse Events v4.0 for grading, is defined as any of the following hematologic toxicities: 1) Grade 4 neutropenia, 2) Grade 3 or 4 febrile neutropenia, 3) thrombocytopenia \<25,000 cells/mm\^3 associated with bleeding and/or which requires platelet transfusion, or any of the following non-hematologic toxicities: 4) any other Grade 4 or 5 toxicity, 5) Grade 3 toxicities lasting \>3 days (exclusions apply), 6) Grade 3 hypertension not controlled by medication, 7) Grade 3 or above gastrointestinal perforation, 8) Grade 3 or above wound dehiscence requiring medical or surgical intervention, 9) any grade thromboembolic event, or 10) any Grade 3 nonhematologic laboratory value if medical intervention is required or the abnormality leads to hospitalization.

    Time frame: Cycle 1; each cycle is 21 days (up to 21 days)

  2. Part 1: Number of Participants Who Experienced 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. The number of participants who experience one of more adverse events during Part 1 of this study will be presented.

    Time frame: Up to approximately 48 months

  3. Part 1: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

    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. The number of participants who discontinue study medication due to and adverse event during Part 1 of this study will be presented.

    Time frame: Up to approximately 58 months

  4. Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

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

    Time frame: Up to approximately 36 months

  5. Part 2: Overall Survival (OS)

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

    Time frame: Up to approximately 47 months

Secondary outcomes

  1. Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    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 as assessed per modified RECIST 1.1 will be presented.

    Time frame: Up to approximately 19 months

  2. Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

    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 per modified RECIST 1.1 will be presented.

    Time frame: Up to approximately 48 months

  3. Part 2: Number of Participants Who Experienced 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. The number of participants who experienced one of more adverse events during Part 2 of this study were presented.

    Time frame: Up to approximately 58 months

  4. Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

    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. The number of participants who discontinued study treatment during Part 2 of this study were presented.

    Time frame: Up to approximately 58 months

  5. Part 2: Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Items 29 and 30) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. 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 each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented

    Time frame: Baseline and Week 27

  6. Part 2: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score

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

    Time frame: Baseline and week 27

  7. Part 2: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score

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

    Time frame: Baseline and Week 27

  8. Part 2: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score

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

    Time frame: Baseline and Week 27

  9. Part 2: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score

    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life.

    Time frame: Baseline and Week 27

  10. Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL) (EORTC QLQ-C30 Items 29 and 30) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS/QoL (EORTC QLQ-C30 Items 29 and 30) 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/QoL score, will be presented. A longer TTD indicates a better outcome.

    Time frame: Baseline and Week 27

  11. Part 2: TTD Based on Change From Baseline in Cough EORTC QLQ-LC13 (Item 31) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline cough (EORTC QLQ-LC30 Items 31) 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 physical functioning score, will be presented. A longer TTD indicates a better outcome.

    Time frame: Baseline And Week 27

  12. Part 2: TTD Based on Change From Baseline in Chest Pain EORTC QLQ-LC13 (Item 40) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline chest pain (EORTC QLQ-C30 Item 40) 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 chest pains core, will be presented. A longer TTD indicates a better outcome.

    Time frame: Baseline and Week 27

  13. Part 2: TTD Based on Change From Baseline in Dyspnea EORTC QLQ-C30 (Item 8) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline dyspnea (EORTC QLQ-C30 Item 8) 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 dyspnea score, will be presented. A longer TTD indicates a better outcome.

    Time frame: Baseline and Week 27

  14. Part 2: TTD Based on Change From Baseline in Physical Functioning EORTC QLQ-C30 (Items 1 Through 5) Score

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline physical functioning (EORTC QLQ-C30 Items 1 through 5) 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 physical functioning score, will be presented. A longer TTD indicates a better outcome.

    Time frame: Baseline and Week 27

  15. Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)

    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in the composite endpoint of cough (QLQ-LC13 item 31), chest pain (QLQ-LC13 item 40), or dyspnea (QLQ-C30 Item 8). 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 the composite endpoint of cough, chest pain or dyspnea, will be presented. A longer TTD indicates a better outcome.

    Time frame: Baseline and Week 27

07

Results

Posted Feb 21, 2025

Participant flow

Participants with treatment-naïve, metastatic nonsquamous Non-small cell lung cancer (NSCLC) were recruited in this study.

Participant flow — Overall Study
MilestonePart 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Started13375373
Treated during first course13373372
Treated during second course135
Completed000
Not completed13375373
Withdrew: Sponsor's decision490102
Withdrew: Withdrawal by subject154
Withdrew: Physician decision030
Withdrew: Lost to follow-up001
Withdrew: Death8277266

Outcome measures

PrimaryPart 1: Number of Participants With a Dose-limiting Toxicity (DLT)

Dose-limiting toxicity using Common Terminology Criteria for Adverse Events v4.0 for grading, is defined as any of the following hematologic toxicities: 1) Grade 4 neutropenia, 2) Grade 3 or 4 febrile neutropenia, 3) thrombocytopenia \<25,000 cells/mm\^3 associated with bleeding and/or which requires platelet transfusion, or any of the following non-hematologic toxicities: 4) any other Grade 4 or 5 toxicity, 5) Grade 3 toxicities lasting \>3 days (exclusions apply), 6) Grade 3 hypertension not controlled by medication, 7) Grade 3 or above gastrointestinal perforation, 8) Grade 3 or above wound dehiscence requiring medical or surgical intervention, 9) any grade thromboembolic event, or 10) any Grade 3 nonhematologic laboratory value if medical intervention is required or the abnormality leads to hospitalization.

Time frame:
Cycle 1; each cycle is 21 days (up to 21 days)
Reported as:
Count of participants · Participants
Part 1: Number of Participants With a Dose-limiting Toxicity (DLT)
ParticipantsPart 1 First Course: Pembrolizumab+Chemotherapy+Lenvatinib
Part 1: Number of Participants With a Dose-limiting Toxicity (DLT)2
PrimaryPart 1: Number of Participants Who Experienced 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. The number of participants who experience one of more adverse events during Part 1 of this study will be presented.

Time frame:
Up to approximately 48 months
Reported as:
Count of participants · Participants
Part 1: Number of Participants Who Experienced an Adverse Event (AE)
ParticipantsPart 1 First Course: Pembrolizumab+Chemotherapy+Lenvatinib
Part 1: Number of Participants Who Experienced an Adverse Event (AE)13
PrimaryPart 1: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

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. The number of participants who discontinue study medication due to and adverse event during Part 1 of this study will be presented.

Time frame:
Up to approximately 58 months
Reported as:
Count of participants · Participants
Part 1: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
ParticipantsPart 1 First Course: Pembrolizumab+Chemotherapy+Lenvatinib
Part 1: Number of Participants Who Discontinued Study Drug Due to an Adverse Event9
PrimaryPart 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

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

Time frame:
Up to approximately 36 months
Reported as:
Median · Months
Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)12.1 (10.4 to 14.1)9.5 (8.3 to 10.7)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.07976 · Hazard ratio (hr): 0.88 · 95% CI 0.74 to 1.05Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.
PrimaryPart 2: Overall Survival (OS)

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

Time frame:
Up to approximately 47 months
Reported as:
Median · Months
Part 2: Overall Survival (OS)
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Overall Survival (OS)21.8 (18.6 to 24.0)22.1 (19.7 to 24.2)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.70818 · Hazard ratio (hr): 1.05 · 95% CI 0.88 to 1.26Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.
SecondaryPart 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

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 as assessed per modified RECIST 1.1 will be presented.

Time frame:
Up to approximately 19 months
Reported as:
Number · Percentage of Participants
Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Percentage of ParticipantsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)57.1 (50.1 to 63.8)50.7 (43.8 to 57.6)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Miettinen & Nurminen · p = 0.08643 · Percent difference: 6.3 · 95% CI -2.8 to 15.4One-sided p-value for testing. H0: difference in percent = 0 versus H1: difference in percent \> 0.
SecondaryPart 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

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 per modified RECIST 1.1 will be presented.

Time frame:
Up to approximately 48 months
Reported as:
Median · Months
Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)1.6 (1.1 to 15.4)1.6 (1.2 to 20.7)
SecondaryPart 2: Number of Participants Who Experienced 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. The number of participants who experienced one of more adverse events during Part 2 of this study were presented.

Time frame:
Up to approximately 58 months
Reported as:
Count of participants · Participants
Part 2: Number of Participants Who Experienced an Adverse Event (AE)
ParticipantsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Number of Participants Who Experienced an Adverse Event (AE)372370
SecondaryPart 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

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. The number of participants who discontinued study treatment during Part 2 of this study were presented.

Time frame:
Up to approximately 58 months
Reported as:
Count of participants · Participants
Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event
ParticipantsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event12792
SecondaryPart 2: Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Items 29 and 30) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. 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 each scored on a 7-point scale (1=Very poor to 7=Excellent). The two raw scores were averaged into a combined score, then normalized using linear transformation so each participant's score ranged from 0 to 100 (0=Worst overall health/quality of life and 100=Best overall health/quality of life). The change from baseline in GHS (EORTC QLQ-C30 Item 29) and QoL (EORTC QLQ-C30 Item 30) combined score is presented

Time frame:
Baseline and Week 27
Reported as:
Least squares mean · Score on a Scale
Part 2: Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Items 29 and 30) Score
Score on a ScalePart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Change From Baseline in Global Health Status (GHS) (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 [EORTC QLQ-C30] Items 29 and 30) Score0.65 (-1.55 to 2.84)1.66 (-0.53 to 3.85)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · t-test, 2 sided · p = 0.4805 · Difference in least square means: -1.01 · 95% CI -3.83 to 1.80
SecondaryPart 2: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score

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

Time frame:
Baseline and week 27
Reported as:
Least squares mean · Score on a scale
Part 2: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score
Score on a scalePart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score-11.77 (-14.72 to -8.81)-11.47 (-14.42 to -8.53)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · t-test, 2 sided · p = 0.8747 · Difference in least square means: -0.29 · 95% CI -3.95 to 3.36
SecondaryPart 2: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score

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

Time frame:
Baseline and Week 27
Reported as:
Least squares mean · Score on a scale
Part 2: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score
Score on a scalePart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score-4.61 (-7.26 to -1.96)-3.70 (-6.34 to -1.06)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · t-test, 2 sided · p = 0.5941 · Difference in least square means: -0.91 · 95% CI -4.24 to 2.43
SecondaryPart 2: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score

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

Time frame:
Baseline and Week 27
Reported as:
Least squares mean · Score on a scale
Part 2: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score
Score on a scalePart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score-2.77 (-6.04 to 0.50)-0.61 (-3.86 to 2.65)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · t-test, 2 sided · p = 0.3115 · Covariate: -2.16 · 95% CI -6.36 to 2.03
SecondaryPart 2: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score

The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 5 questions about their physical functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) score will be presented. A higher score indicates a better quality of life.

Time frame:
Baseline and Week 27
Reported as:
Least squares mean · Score on a scale
Part 2: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score
Score on a scalePart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score-4.11 (-6.37 to -1.84)-3.73 (-5.99 to -1.48)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · t-test, 2 sided · p = 0.8134 · Covariate: -0.37 · 95% CI -3.47 to 2.72
SecondaryPart 2: Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL) (EORTC QLQ-C30 Items 29 and 30) Score

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS/QoL (EORTC QLQ-C30 Items 29 and 30) 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/QoL score, will be presented. A longer TTD indicates a better outcome.

Time frame:
Baseline and Week 27
Reported as:
Median · Months
Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL) (EORTC QLQ-C30 Items 29 and 30) Score
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)/Quality of Life (QoL) (EORTC QLQ-C30 Items 29 and 30) Score15.70 (9.66 to NA)NA (21.32 to NA)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.2133 · Hazard ratio (hr): 1.16 · 95% CI 0.92 to 1.47Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.
SecondaryPart 2: TTD Based on Change From Baseline in Cough EORTC QLQ-LC13 (Item 31) Score

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline cough (EORTC QLQ-LC30 Items 31) 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 physical functioning score, will be presented. A longer TTD indicates a better outcome.

Time frame:
Baseline And Week 27
Reported as:
Median · Months
Part 2: TTD Based on Change From Baseline in Cough EORTC QLQ-LC13 (Item 31) Score
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: TTD Based on Change From Baseline in Cough EORTC QLQ-LC13 (Item 31) ScoreNA (NA to NA)NA (NA to NA)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.0377 · Hazard ratio (hr): 1.41 · 95% CI 1.02 to 1.94Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.
SecondaryPart 2: TTD Based on Change From Baseline in Chest Pain EORTC QLQ-LC13 (Item 40) Score

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline chest pain (EORTC QLQ-C30 Item 40) 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 chest pains core, will be presented. A longer TTD indicates a better outcome.

Time frame:
Baseline and Week 27
Reported as:
Median · Months
Part 2: TTD Based on Change From Baseline in Chest Pain EORTC QLQ-LC13 (Item 40) Score
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: TTD Based on Change From Baseline in Chest Pain EORTC QLQ-LC13 (Item 40) ScoreNA (NA to NA)NA (NA to NA)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.4084 · Hazard ratio (hr): 0.87 · 95% CI 0.62 to 1.21Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.
SecondaryPart 2: TTD Based on Change From Baseline in Dyspnea EORTC QLQ-C30 (Item 8) Score

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline dyspnea (EORTC QLQ-C30 Item 8) 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 dyspnea score, will be presented. A longer TTD indicates a better outcome.

Time frame:
Baseline and Week 27
Reported as:
Median · Months
Part 2: TTD Based on Change From Baseline in Dyspnea EORTC QLQ-C30 (Item 8) Score
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: TTD Based on Change From Baseline in Dyspnea EORTC QLQ-C30 (Item 8) ScoreNA (NA to NA)NA (NA to NA)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.7955 · Hazard ratio (hr): 1.04 · 95% CI 0.79 to 1.36Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.
SecondaryPart 2: TTD Based on Change From Baseline in Physical Functioning EORTC QLQ-C30 (Items 1 Through 5) Score

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline physical functioning (EORTC QLQ-C30 Items 1 through 5) 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 physical functioning score, will be presented. A longer TTD indicates a better outcome.

Time frame:
Baseline and Week 27
Reported as:
Median · Months
Part 2: TTD Based on Change From Baseline in Physical Functioning EORTC QLQ-C30 (Items 1 Through 5) Score
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: TTD Based on Change From Baseline in Physical Functioning EORTC QLQ-C30 (Items 1 Through 5) Score16.82 (8.84 to 22.51)NA (NA to NA)
SecondaryPart 2: Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)

TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in the composite endpoint of cough (QLQ-LC13 item 31), chest pain (QLQ-LC13 item 40), or dyspnea (QLQ-C30 Item 8). 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 the composite endpoint of cough, chest pain or dyspnea, will be presented. A longer TTD indicates a better outcome.

Time frame:
Baseline and Week 27
Reported as:
Median · Months
Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)
MonthsPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+Placebo
Part 2: Time to True Deterioration (TTD) Based on Change From Baseline in the Composite Endpoint of Cough (EORTC QLQ-LC13 Item 31), Chest Pain (EORTC QLQ-LC13 Item 40), or Dyspnea (EORTC QLQ-C30 Item 8)8.28 (5.98 to 11.07)9.33 (7.03 to 12.91)
Statistical analysis
  • Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib vs Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo · Stratified Log Rank · p = 0.7191 · Hazard ratio (hr): 1.04 · 95% CI 0.84 to 1.28Two-sided p-value based on log-rank test stratified by ECOG performance status, geographic region of the enrolling site, and baseline PD-L1 status.

Adverse events

Collected over Up to approximately 58 months. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part 1 First Course: Pembrolizumab+Chemotherapy+Lenvatinib9/13 (69.2%)7/13 (53.8%)13/13 (100%)
Part 2 First Course: Pembrolizumab+Chemotherapy+Lenvatinib278/375 (74.1%)232/373 (62.2%)366/373 (98.1%)
Part 2 First Course: Pembrolizumab+Chemotherapy+Placebo266/373 (71.3%)189/372 (50.8%)363/372 (97.6%)
Part 1 Second Course: Pembrolizumab Only From Pembrolizumab+Chemotherapy+Lenvatinib0/1 (0%)1/1 (100%)1/1 (100%)
Part 2 Second Course: Pembrolizumab+Chemotherapy+Lenvatinib3/3 (100%)1/3 (33.3%)2/3 (66.7%)
Part 2 Second Course: Pembrolizumab+Chemotherapy+Placebo3/7 (42.9%)3/7 (42.9%)4/7 (57.1%)
Most frequent serious events
Showing 10 of 270
Most frequent serious events
EventPart 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboPart 1 Second Course: Pembrolizumab Only From Pembrolizumab+Chemotherapy+LenvatinibPart 2 Second Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 Second Course: Pembrolizumab+Chemotherapy+Placebo
HyponatraemiaMetabolism and nutrition disorders0/133/3733/3721/10/30/7
Cardiac arrestCardiac disorders0/131/3730/3720/11/30/7
SyncopeNervous system disorders0/131/3731/3720/11/30/7
PneumoniaInfections and infestations2/1328/37336/3720/10/31/7
Sensory disturbanceNervous system disorders0/130/3730/3720/10/31/7
Pleural effusionRespiratory, thoracic and mediastinal disorders1/1310/3739/3720/10/31/7
Pulmonary embolismRespiratory, thoracic and mediastinal disorders0/1311/3738/3720/10/31/7
AnaemiaBlood and lymphatic system disorders1/1317/3739/3720/10/30/7
Atrial fibrillationCardiac disorders1/132/3732/3720/10/30/7
Adrenal insufficiencyEndocrine disorders1/133/3730/3720/10/30/7
Most frequent other events
Showing 10 of 160
Most frequent other events
EventPart 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboPart 1 Second Course: Pembrolizumab Only From Pembrolizumab+Chemotherapy+LenvatinibPart 2 Second Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 Second Course: Pembrolizumab+Chemotherapy+Placebo
DiarrhoeaGastrointestinal disorders7/13127/37369/3721/10/30/7
DizzinessNervous system disorders3/1339/37336/3721/10/30/7
NauseaGastrointestinal disorders10/13148/373137/3720/10/30/7
HypertensionVascular disorders9/13110/37344/3720/11/31/7
FatigueGeneral disorders8/13116/37386/3720/10/30/7
AnaemiaBlood and lymphatic system disorders1/13192/373220/3720/11/30/7
ConstipationGastrointestinal disorders7/13120/373110/3720/11/30/7
Neutrophil count decreasedInvestigations4/13188/373154/3720/10/30/7
Back painMusculoskeletal and connective tissue disorders6/1344/37342/3720/10/30/7
Platelet count decreasedInvestigations1/13148/37398/3720/10/30/7

Baseline characteristics

Age, Continuous
Age, Continuous(Years)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
Mean64.2 ± 7.662.0 ± 9.963.0 ± 9.762.5 ± 9.8
Sex: Female, Male
Sex: Female, Male(Participants)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
Female6121126253
Male7254247508
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
Hispanic or Latino07577152
Not Hispanic or Latino13291279583
Unknown or Not Reported091726
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
American Indian or Alaska Native0011
Asian5116114235
Native Hawaiian or Other Pacific Islander0213
Black or African American0033
White8248237493
More than one race0000
Unknown or Not Reported091726
Eastern Cooperative Oncology Group (ECOG) Performance Status
Eastern Cooperative Oncology Group (ECOG) Performance Status(Participants)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
ECOG = 08135133276
ECOG = 15240240485
Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline
Programmed Cell Death Ligand 1 (PD-L1) Status at Baseline(Participants)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
TPS = < 50%10272269551
TPS = ≥ 50%39091184
Not Evaluable0131326
Geographic Region
Geographic Region(Participants)Part 1 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+LenvatinibPart 2 First Course: Pembrolizumab+Chemotherapy+PlaceboTotal
East Asia3111112226
Non-East Asia10264261535
08

Study locations

158 sites
  • El Camino Hospital Cancer Center ( Site 0529)
    Mountain View, California 94040, United States
  • Yale University ( Site 0519)
    New Haven, Connecticut 06520-8028, United States
  • Holy Cross Hospital ( Site 0512)
    Fort Lauderdale, Florida 33308, United States
  • Mercy Health-Paducah Medical Oncology and Hematology ( Site 0570)
    Paducah, Kentucky 42003, United States
  • Henry Ford Health System ( Site 0563)
    Detroit, Michigan 48202, United States
  • Saint Lukes Cancer Institute ( Site 0541)
    Kansas City, Missouri 64111, United States
  • Broome Oncology, LLC ( Site 0562)
    Johnson City, New York 13790, United States
  • Sanford Health Roger Maris Cancer Center ( Site 0533)
    Fargo, North Dakota 58122, United States
  • Stephenson Cancer Center ( Site 0504)
    Oklahoma City, Oklahoma 73104, United States
  • Good Samaritan Hospital Corvallis ( Site 0521)
    Corvallis, Oregon 97330, United States
  • Thomas Jefferson University Hospital ( Site 0548)
    Philadelphia, Pennsylvania 19107, United States
  • Abington Hospital - Asplundh Cancer Center ( Site 0575)
    Willow Grove, Pennsylvania 19090, United States
  • West Cancer Center - East Campus ( Site 0544)
    Germantown, Tennessee 38138, United States
  • Parkland Health & Hospital System ( Site 0576)
    Dallas, Texas 75235, United States
  • UT Southwestern Medical Center ( Site 0558)
    Dallas, Texas 75390, United States
  • Utah Cancer Specialists ( Site 0523)
    Salt Lake City, Utah 84106, United States
  • West Virginia University ( Site 0526)
    Morgantown, West Virginia 26506, United States
  • Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 0367)
    Berazategui, Buenos Aires B1884BBF, Argentina
  • Instituto de Investigaciones Clinicas Mar del Plata ( Site 0371)
    Mar del Plata, Buenos Aires B7600FZO, Argentina
  • CEMIC ( Site 0370)
    Buenos Aires, Buenos Aires F.D. C1431FWO, Argentina
  • Sanatorio Parque ( Site 0365)
    Rosario, Santa Fe Province S2000DSV, Argentina
  • Hospital Aleman ( Site 0368)
    Buenos Aires, C1118AAT, Argentina
  • Instituto Medico Especializado Alexander Fleming ( Site 0369)
    Buenos Aires, C1426ANZ, Argentina
  • CEMAIC ( Site 0374)
    Córdoba, X5008HHW, Argentina
  • CER San Juan Centro Polivalente de Asistencia e Investigacion Clinica ( Site 0372)
    San Juan, J5402DIL, Argentina
  • Blacktown Hospital Western Sydney Local Health District ( Site 0008)
    Blacktown, New South Wales 2148, Australia
  • Port Macquarie Base Hospital ( Site 0001)
    Port Macquarie, New South Wales 2444, Australia
  • Chris OBrien Lifehouse ( Site 0006)
    Sydney, New South Wales 2050, Australia
  • Westmead Hospital ( Site 0009)
    Sydney, New South Wales 2145, Australia
  • Cairns Hospital ( Site 0002)
    Cairns, Queensland 4870, Australia
  • The Prince Charles Hospital ( Site 0010)
    Chermside, Queensland 4032, Australia
  • Ballarat Health Services ( Site 0003)
    Ballarat, Victoria 3350, Australia
  • Moncton Hospital - Horizon Health Network ( Site 0410)
    Moncton, New Brunswick E1C 6Z8, Canada
  • Juravinski Cancer Centre ( Site 0407)
    Hamilton, Ontario L8V 1C3, Canada
  • Kingston Health Sciences Centre ( Site 0414)
    Kingston, Ontario K7L 2V7, Canada
  • Lakeridge Health ( Site 0406)
    Oshawa, Ontario L1G 2B9, Canada
  • Sault Area Hospital ( Site 0413)
    Sault Ste. Marie, Ontario P6B 0A8, Canada
  • Hopital Cite de la Sante de Laval ( Site 0400)
    Laval, Quebec H7M 3L9, Canada
  • CIUSSS Ouest de l Ile - St-Mary s Hospital ( Site 0412)
    Montreal, Quebec H3T 1M5, Canada
  • CHU de Quebec-Universite Laval-Hotel Dieu de Quebec ( Site 0403)
    Québec, Quebec G1R 2J6, Canada
  • CIUSSS de la Mauricie et du Centre du Quebec ( Site 0408)
    Trois-Rivières, Quebec G8Z 3R9, Canada
  • Centro de Investigacion y desarrollo Oncologico SpA - CIDO SpA ( Site 0380)
    Temuco, Araucania 4810218, Chile
  • Clinica Universidad Catolica del Maule ( Site 0385)
    Talca, Maule Region 3465584, Chile
  • OrlandiOncologia ( Site 0381)
    Santiago, Region M. de Santiago 7500713, Chile
  • Fundacion Arturo Lopez Perez FALP ( Site 0383)
    Santiago, Region M. de Santiago 7500921, Chile
  • Pontificia Universidad Catolica de Chile ( Site 0382)
    Santiago, Region M. de Santiago 8330032, Chile
  • Bradford Hill Centro de Investigaciones Clinicas ( Site 0387)
    Santiago, Region M. de Santiago 8420383, Chile
  • Oncocentro ( Site 0384)
    Viña del Mar, Valparaiso 2520598, Chile
  • Centro Oncologico Antofagasta ( Site 0386)
    Antofagasta, 1240000, Chile
  • Peking Union Medical College Hospital ( Site 0108)
    Beijing, Beijing Municipality 100006, China
  • Cancer Hospital Chinese Academy of Medical Science ( Site 0117)
    Beijing, Beijing Municipality 100021, China
  • Beijing Cancer Hospital ( Site 0120)
    Beijing, Beijing Municipality 100036, China
  • The Second Hospital Affiliated to AMU ( Site 0119)
    Chongqing, Chongqing Municipality 400037, China
  • First Affiliated Hospital of The Third Military Medical University ( Site 0118)
    Chongqing, Chongqing Municipality 400038, China
  • Fujian Provincial Cancer Hospital ( Site 0102)
    Fuzhou, Fujian 350014, China
  • Southern Medical University Nanfang Hospital ( Site 0121)
    Guangzhou, Guangdong 510515, China
  • The Third Affiliated Hospital of Harbin Medical University ( Site 0100)
    Harbin, Heilongjiang 150081, China
  • Henan Cancer Hospital ( Site 0112)
    Zhengzhou, Henan 450008, China
  • Wuhan Union Hospital Cancer Center-Cancer Center ( Site 0123)
    Wuhan, Hubei 430022, China
  • Hubei Cancer Hospital ( Site 0122)
    Wuhan, Hubei 430079, China
  • Jilin Cancer Hospital ( Site 0115)
    Changchun, Jilin 130103, China
  • Zhongshan Hospital Fudan University ( Site 0103)
    Shanghai, Shanghai Municipality 200032, China
  • Shanghai Pulmonary Hospital ( Site 0101)
    Shanghai, Shanghai Municipality 200443, China
  • Tianjin Medical University Cancer Institute & Hospital ( Site 0111)
    Tianjin, Tianjin Municipality 300060, China
  • Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0110)
    Urumuqi, Xinjiang 830000, China
  • The First Affiliated Hospital Zhejiang University ( Site 0109)
    Hangzhou, Zhejiang 310003, China
  • Zhejiang Cancer Hospital ( Site 0113)
    Hangzhou, Zhejiang 310022, China
  • The First Affiliated Hospital of Wenzhou Medical University ( Site 0124)
    Wenzhou, Zhejiang 325000, China
  • Hopital Cardiologique Louis Pradel ( Site 0141)
    Bron, Auvergne-Rhône-Alpes 69500, France
  • Centre Paul Strauss ( Site 0144)
    Strasbourg, Bas-Rhin 67065, France
  • Hopital Nord du Marseille ( Site 0147)
    Marseille, Bouches-du-Rhone 13015, France
  • Hopital Foch ( Site 0145)
    Suresnes, Hauts-de-Seine 92151, France
  • Centre de Cancerologie du Grand Montpellier ( Site 0142)
    Montpellier, Herault 34070, France
  • Hopital Laennec ( Site 0146)
    Nantes, Loire-Atlantique 44093, France
  • Hopital Robert Schuman ( Site 0143)
    Vantoux, Moselle 57070, France
  • L'hopital Nord-Ouest - Centre Hospitalier de Villefranche sur Saone ( Site 0149)
    Villefranche-sur-Saône, Rhone 69655, France
  • Hopital Cochin ( Site 0140)
    Paris, 75014, France
  • Klinikum Esslingen GmbH ( Site 0164)
    Esslingen am Neckar, Baden-Wurttemberg 73730, Germany
  • Krankenhaus Nordwest ( Site 0169)
    Frankfurt am Main, Hesse 60488, Germany
  • Pius Hospital Oldenburg ( Site 0170)
    Oldenburg, Lower Saxony 26121, Germany
  • Uniklinik RWTH Aachen ( Site 0160)
    Aachen, North Rhine-Westphalia 52074, Germany
  • Universitaetsklinikum des Saarlandes ( Site 0165)
    Homburg, Saarland 66421, Germany
  • Krankenhaus Martha Maria Halle-Doelau ( Site 0166)
    Halle, Saxony-Anhalt 06120, Germany
  • LungenClinic Grosshansdorf GmbH ( Site 0171)
    Großhansdorf, Schleswig-Holstein 22927, Germany
  • Hamato-Onkologie Hamburg Prof. Laack und Partner ( Site 0161)
    Hamburg, 20251, Germany
  • Soroka Medical Center ( Site 0222)
    Beersheba, 8410101, Israel
  • Rambam Medical Center ( Site 0223)
    Haifa, 3109601, Israel
  • Shaare Zedek Medical Center-Oncology ( Site 0229)
    Jerusalem, 9013102, Israel
  • Meir Medical Center ( Site 0221)
    Kfar Saba, 4428164, Israel
  • Holy Family Hospital ( Site 0228)
    Nazareth, 1641101, Israel
  • Rabin Medical Center ( Site 0224)
    Petah Tikva, 4941492, Israel
  • Sheba Medical Center ( Site 0220)
    Ramat Gan, 5262000, Israel
  • Sourasky Medical Center ( Site 0225)
    Tel Aviv, 6423906, Israel
  • Shamir Medical Center-Assaf Harofeh ( Site 0227)
    Ẕerifin, 70300, Israel
  • National Hospital Organization Nagoya Medical Center ( Site 0017)
    Nagoya, Aichi-ken 460-0001, Japan
  • Fujita Health University Hospital ( Site 0016)
    Toyoake, Aichi-ken 470-1192, Japan
  • National Cancer Center Hospital East ( Site 0024)
    Kashiwa, Chiba 277-8577, Japan
  • Kanazawa University Hospital ( Site 0018)
    Kanazawa, Ishikawa-ken 920-8641, Japan
  • Osaka Habikino Medical Center ( Site 0020)
    Habikino, Osaka 583-8588, Japan
  • Kansai Medical University Hospital ( Site 0022)
    Hirakata, Osaka 573-1191, Japan

Showing the first 100 of 158 sites across 17 countries.

09

References and documents

Publications

  • Herbst RS, Cho BC, Zhou C, Burotto M, Dols MC, Sendur MAN, Moiseyenko V, Casarini I, Nishio M, Hui R, Pons-Tostivint E, Dudnik J, Ahmed S, Okpara CE, Dutcus C, Yin L, Luo Y, Chirovsky D, Bhagwati N, Abreu DR. Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 LEAP-006 Study. J Thorac Oncol. 2025 Sep;20(9):1302-1314. doi: 10.1016/j.jtho.2025.05.016. Epub 2025 May 24. PubMed 40419140 ↗

Study documents

  • Protocol and statistical analysis plan · Oct 27, 2023

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

Individual participant data

Plan to share: Yes — http://engagezone.msd.com/doc/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
NCT03829319
Lead sponsor
Merck Sharp & Dohme LLC
Collaborators
Eisai Inc.
Responsible party
Sponsor
First posted
Feb 4, 2019
Start date
Mar 25, 2019
Primary completion
Aug 11, 2023
Completion
Aug 30, 2024
Results posted
Feb 21, 2025
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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