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Trial record 1 of 1 for:    NCT03829332
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Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Non-small Cell Lung Cancer (NSCLC)(MK-7902-007/E7080-G000-314/LEAP-007)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03829332
Recruitment Status : Recruiting
First Posted : February 4, 2019
Last Update Posted : October 22, 2020
Sponsor:
Collaborator:
Eisai Inc.
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Tracking Information
First Submitted Date  ICMJE February 1, 2019
First Posted Date  ICMJE February 4, 2019
Last Update Posted Date October 22, 2020
Actual Study Start Date  ICMJE March 13, 2019
Estimated Primary Completion Date March 8, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 24 months ]
    PFS is 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, 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. PFS as assessed per RECIST 1.1 will be presented.
  • Overall Survival (OS) [ Time Frame: Up to approximately 60 months ]
    OS is defined as the time from date of randomization to date of death from any cause. OS will be presented.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2019)
  • Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 24 months ]
    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. ORR as assessed per RECIST 1.1 will be presented.
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Through 90 days post last dose of study treatment (Up to approximately 27 months) ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
  • Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Through last dose of study treatment (Up to approximately 24 months) ]
    The number of participants who discontinue study treatment due to an AE will be presented.
  • 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] Item 29) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question "How would you rate your overall health 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) score will be presented. A higher score indicates a better overall GHS.
  • Change from Baseline in Quality of Life (QoL)(EORTC QLQ-C30 Item 30) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to the question " 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 QoL (EORTC QLQ-C30 Item 30) score will be presented. A higher score indicates a better overall QoL.
  • Change from Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    The EORTC QLQ-LC13 is a lung cancer-specific supplemental questionnaire used in combination with the EORTC QLQ-C30. Participant responses to the question "How much did you cough?" are scored on a 4-point scale (1=Not at All to 4=Very Much). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The change from baseline in cough (EORTC QLQ-LC13 Item 31) score will be presented. A lower score indicates a better outcome.
  • Change from Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    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.
  • Change from Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    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.
  • Change from Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    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 to True Deterioration (TTD) Based on Change from Baseline in Global Health Status (GHS)(EORTC QLQ-C30 Item 29) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS (EORTC QLQ-C30 Item 29) 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 score, will be presented. A longer TTD indicates a better outcome.
  • Time to True Deterioration (TTD) Based on Change from Baseline in Quality of Life (QoL)(EORTC QLQ-C30 Item 30) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in QoL (EORTC QLQ-C30 Item 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 QoL score, will be presented. A longer TTD indicates a better outcome.
  • Time to True Deterioration (TTD) Based on Change from Baseline in the Composite Endpoint of Cough & Chest Pain (EORTC QLQ-LC13 Items 31 & 40) or Dyspnea (EORTC QLQ-C30 Item 8) [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    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 & chest pain (EORTC QLQ-LC13 Items 31 & 40) & dyspnea (EORTC 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 to True Deterioration (TTD) Based on Change from Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in physical functioning (EORTC QLQ-C30 Items 1-5) 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 1, 2019)
  • Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Up to approximately 24 months ]
    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. ORR as assessed per RECIST 1.1 will be presented.
  • Number of Participants Who Experience an Adverse Event (AE) [ Time Frame: Through 90 days post last dose of study treatment (Up to approximately 27 months) ]
    An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be presented.
  • Number of Participants Who Discontinue Study Treatment Due to an Adverse Event (AE) [ Time Frame: Through last dose of study treatment (Up to approximately 24 months) ]
    The number of participants who discontinue study treatment due to an AE will be presented.
  • Change from Baseline in Global Health Status (GHS), Quality of Life (QoL), Cough, Chest Pain, Dyspnea and Physical Functioning Combined Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC) QLQ-C30 is a questionnaire to assess the overall QoL of cancer patients. The EORTC QLQ Lung Cancer Module 13 (QLQ-LC13) is a supplemental lung cancer-specific module used in combination with QLQ-C30. The change from baseline in EORTC QLQ-C30 GHS/QoL (EORTC QLQ-C30 Items 29 and 30); Cough (EORTC QLQ-LC13 Item 31); Chest Pain (EORTC QLQ-LC13 Item 40); Dyspnea (EORTC QLQ-C30 Item 8); and Physical Functioning (EORTC QLQ-C30 Items 1-5) combined score will be presented. A higher combined score indicates a better QoL.
  • Time to True Deterioration (TTD) as Assessed by Change from Baseline in Global Health Status (GHS), Quality of Life (QoL), Cough, Chest Pain, Dyspnea and Physical Functioning Combined Score [ Time Frame: Baseline (Cycle 1 Day 1: Predose) and at designated timepoints (Predose) up to 30 days post last dose. Each cycle is 21 days. (Up to approximately 25 months) ]
    TTD is defined as the time from Baseline to the first onset of a ≥10-point negative change (decrease) from Baseline in GHS/QoL (European Organization for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire-Core 30 [QLQ-C30] Items 29 and 30), cough (EORTC QLQ Lung Cancer Module 13 [QLQ-LC13] Item 31), chest pain (EORTC QLQ-LC13 Item 40), dyspnea (EORTC QLQ-LC13 Item 8), and physical functioning (EORTC QLQ-C30 Items 1-5) The TTD, as assessed based on a ≥10-point negative change (decrease) from Baseline in combined score, will be presented.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) in Adults With Programmed Cell Death-Ligand 1 (PD-L1)-Positive Treatment-naïve Non-small Cell Lung Cancer (NSCLC)(MK-7902-007/E7080-G000-314/LEAP-007)
Official Title  ICMJE A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naïve, Metastatic Non-small Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)
Brief Summary

The purpose of this study is to assess the safety and efficacy of pembrolizumab (MK-3475) combined with lenvatinib (MK-7902/E7080) compared to pembrolizumab alone (with placebo for lenvatinib) in treatment-naïve adults with no prior systemic therapy for their metastatic non-small cell lung cancer (NSCLC) whose tumors have a programmed cell death-ligand 1 (PD-L1) Tumor Proportion Score (TPS) greater than or equal to 1%.

The primary study hypotheses are that: 1) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and 2) The combination of pembrolizumab and lenvatinib is superior to pembrolizumab alone as assessed by Overall Survival (OS).

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Non-small Cell Lung Cancer
Intervention  ICMJE
  • Biological: Pembrolizumab
    IV infusion
    Other Names:
    • MK-3475
    • KEYTRUDA®
  • Drug: Lenvatinib
    oral capsule
    Other Names:
    • MK-7902
    • E7080
    • LENVIMA®
  • Drug: Placebo for lenvatinib
    oral capsule
Study Arms  ICMJE
  • Experimental: Pembrolizumab + Lenvatinib
    Participants receive pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS lenvatinib 20 mg via oral capsule once daily (QD) on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Lenvatinib
  • Active Comparator: Pembrolizumab + Placebo
    Participants receive pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 administrations (up to approximately 2 years) PLUS placebo for lenvatinib via oral capsule QD on Days 1-21 of each 3-week cycle until progressive disease or unacceptable toxicity.
    Interventions:
    • Biological: Pembrolizumab
    • Drug: Placebo for lenvatinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 1, 2019)
620
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 8, 2024
Estimated Primary Completion Date March 8, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Has a histologically or cytologically confirmed diagnosis of NSCLC.
  • Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC]).
  • Has measurable disease based on RECIST 1.1.
  • Has tumor tissue that demonstrates programmed cell death-ligand 1 (PD-L1) expression in ≥1% of tumor cells (Tumor Proportion Score [TPS] ≥1%) as assessed by immunohistochemistry (IHC) 22C3 pharmDx assay (Dako North America, Inc.) at a central laboratory.
  • Has a life expectancy of ≥3 months.
  • Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days before the first dose of study treatment but before randomization.
  • Male participants must agree to the following during the treatment period and for ≥30 days after the last dose of lenvatinib/matching placebo: 1) Be abstinent from heterosexual intercourse as their preferred and usual lifestyle and agree to remain abstinent, OR 2) Must agree to use contraception unless confirmed to be azoospermic (vasectomized or secondary to medical cause).
  • Female participants are eligible to participate if not pregnant or breastfeeding, and ≥1 of the following applies: 1) Is not a woman of child-bearing potential (WOCBP), OR 2) Is a WOCBP and is using a highly effective contraceptive method that has a low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle during the treatment period and for ≥120 days post pembrolizumab or ≥30 days post lenvatinib/matching placebo, whichever occurs last.
  • Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mm Hg and no change in antihypertensive medications within 1 week before randomization.
  • Has adequate organ function.

Exclusion Criteria:

  • Has known untreated central nervous system metastases and/or carcinomatous meningitis.
  • Has a known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for ≥3 years since initiation of that therapy. (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, squamous cell carcinoma of the skin, in situ cervical cancer, or other in situ cancers.)
  • Has an active autoimmune disease that has required systemic treatment in the past 2 years. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
  • Has had an allogeneic tissue/solid organ transplant.
  • Has a known history of human immunodeficiency virus (HIV) infection.
  • Has a history of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
  • Has a known history of hepatitis B or known active hepatitis C virus infection.
  • Has a history of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral study drug absorption.
  • Has significant cardiovascular impairment within 12 months of the first dose of study treatment, such as a history of congestive heart failure greater than New York Heart Association Class II, unstable angina, myocardial infarction, cerebrovascular accident/stroke, or cardiac arrhythmia associated with hemodynamic instability.
  • Has not recovered adequately from any toxicity and/or complications from major surgery before starting study treatment.
  • Has a known history of active tuberculosis (TB).
  • Has an active infection requiring systemic therapy.
  • Has previously had a severe hypersensitivity reaction to treatment with a monoclonal antibody or has a known sensitivity or intolerance to any component of lenvatinib or pembrolizumab.
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study treatment.
  • Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their metastatic NSCLC.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], Tumor necrosis factor receptor superfamily, member 4 [OX 40], tumor necrosis factor receptor superfamily member 9 [CD137]) or has received lenvatinib as monotherapy or in combination with anti- programmed cell death protein (anti-PD-1) agents.
  • Has received radiotherapy within 14 days before the first dose of study treatment or received lung radiation therapy of >30 Gray (Gy) within 6 months before the first dose of study treatment. (Note: Participants must have recovered from all radiation-related toxicities to ≤Grade 1, not require corticosteroids, and not have had radiation pneumonitis.)
  • Has a diagnosis of immunodeficiency or is receiving any form of immunosuppressive therapy within 7 days before the first dose of study treatment.
  • Is receiving systemic steroid therapy (doses >10 mg daily of prednisone equivalent) within 7 days before the first dose of study treatment.
  • Has received a live vaccine within 30 days before the first dose of study treatment.
  • Has had major surgery within 3 weeks prior to first dose of study treatment
  • Has pre-existing ≥Grade 3 gastrointestinal or non-gastrointestinal fistula.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com
Listed Location Countries  ICMJE Australia,   Canada,   China,   Colombia,   Estonia,   France,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Malaysia,   Mexico,   Poland,   Russian Federation,   Taiwan,   Turkey,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03829332
Other Study ID Numbers  ICMJE 7902-007
MK-7902-007 ( Other Identifier: Merck Protocol Number )
E7080-G000-314 ( Other Identifier: Eisai Protocol Number )
LEAP-007 ( Other Identifier: Merck )
2018-003794-98 ( EudraCT Number )
194670 ( Registry Identifier: JAPIC-CTI )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php
Responsible Party Merck Sharp & Dohme Corp.
Study Sponsor  ICMJE Merck Sharp & Dohme Corp.
Collaborators  ICMJE Eisai Inc.
Investigators  ICMJE
Study Director: Medical Director Merck Sharp & Dohme Corp.
PRS Account Merck Sharp & Dohme Corp.
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP