A Phase 3, Randomized, Double-blind Trial of Pembrolizumab (MK-3475) With or Without Lenvatinib (E7080/MK-7902) in Participants With Treatment-naïve, Metastatic Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 623
- 试验地点
- 162
- 主要终点
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
研究概览
简要总结
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).
详细描述
As of 30-Jul-2021, active participants, investigator, and sponsor personnel or delegate(s) involved in the treatment administration or clinical evaluation of the participants will be unblinded. Participants will discontinue lenvatinib and placebo, and participants who remain on treatment will receive open-label pembrolizumab only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Has a histologically or cytologically confirmed diagnosis of non-small cell lung cancer (NSCLC)
- •Has Stage IV NSCLC (American Joint Committee on Cancer [AJCC 8th edition])
- •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 ≥7 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
排除标准
- •Has known untreated central nervous system metastases and/or carcinomatous meningitis
- •Has active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention
- •Has radiographic evidence of intratumoral cavitations, encasement, or invasion of a major blood vessel
- •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
- •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 or attenuated 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 nongastrointestinal fistula
研究组 & 干预措施
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.
干预措施: Pembrolizumab (Biological)
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.
干预措施: Lenvatinib (Drug)
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.
干预措施: Pembrolizumab (Biological)
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.
干预措施: Placebo for lenvatinib (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
时间窗: Up to approximately 25 months
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. 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 was presented.
Overall Survival (OS)
时间窗: Up to approximately 25 months
OS was defined as the time from date of randomization to date of death from any cause. OS was presented.
次要结局
- Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)(Up to approximately 25 months)
- Number of Participants Who Experienced an Adverse Event (AE)(Through 90 days post last dose of study treatment (Up to approximately 27 months))
- Number of Participants Who Discontinued Study Treatment Due to an Adverse Event (AE)(Through last dose of study treatment (Up to approximately 24 months))
- Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core30 (QLQ-C30) Combined Global Health Status/Quality of Life (Items 29 & 30) Scale Combined Score(Baseline and Week 21)
- Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score(Baseline and Week 21)
- Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score(Baseline and Week 21)
- Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score(Baseline and Week 21)
- Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score(Baseline and Week 21)
- Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status /Quality of Life (Items 29 & 30) Scale Combined Score(Up to approximately 25 months)
- Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score(Up to approximately 25 months)
- Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score(Up to approximately 25 months)
- Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score(Up to approximately 25 months)
- Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score(Up to approximately 25 months)
- 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)(Up to approximately 25 months)