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)
Overview
- Phase
- Phase 3
- Intervention
- Pembrolizumab
- Conditions
- Non-small Cell Lung Cancer
- Sponsor
- Merck Sharp & Dohme LLC
- Enrollment
- 623
- Locations
- 162
- Primary Endpoint
- Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
- Status
- Completed
- Last Updated
- 2 months ago
Overview
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
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Pembrolizumab
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.
Intervention: Lenvatinib
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.
Intervention: Pembrolizumab
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.
Intervention: Placebo for lenvatinib
Outcomes
Primary Outcomes
Progression-free Survival (PFS) as Assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- 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)