Clinical Trials /

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)

NCT03829332

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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)

Clinical Trial IDs

  • ORG STUDY ID: 7902-007
  • SECONDARY ID: MK-7902-007
  • SECONDARY ID: E7080-G000-314
  • SECONDARY ID: LEAP-007
  • SECONDARY ID: 2018-003794-98
  • NCT ID: NCT03829332

Conditions

  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
PembrolizumabMK-3475, KEYTRUDA®Pembrolizumab + Lenvatinib
LenvatinibMK-7902, E7080, LENVIMA®Pembrolizumab + Lenvatinib
Placebo for lenvatinibPembrolizumab + Placebo

Purpose

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 the treatment 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).

Trial Arms

NameTypeDescriptionInterventions
Pembrolizumab + LenvatinibExperimentalParticipants 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.
  • Pembrolizumab
  • Lenvatinib
Pembrolizumab + PlaceboActive ComparatorParticipants 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.
  • Pembrolizumab
  • Placebo for lenvatinib

Eligibility Criteria

        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 at
             least 120 days after the last dose of study treatment: 1.) Must be abstinent from
             heterosexual intercourse as their preferred and usual lifestyle and agree to remain
             abstinent OR 2.) Must agree to use study-approved contraception unless confirmed to be
             azoospermic (vasectomized or secondary to medical cause) AND 3.) Must refrain from
             donating sperm for at least 120 days after the last dose of lenvatinib.

          -  Female participants are eligible if they are not pregnant or breastfeeding, and ≥1 of
             the following conditions applies: 1.) Is not a WOCBP OR 2.) Is a WOCBP and using a
             study-approved contraceptive method, or be abstinent from heterosexual intercourse as
             their preferred and usual lifestyle, during the treatment period and for at least 120
             days after the last dose of study treatment.

          -  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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure: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
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure: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
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description:The number of participants who discontinue study treatment due to an AE will be presented.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.
Measure: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)
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Merck Sharp & Dohme Corp.

Trial Keywords

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

Last Updated