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 Nonsmall Cell Lung Cancer (NSCLC) [MK-7902-007/E7080-G000-314/LEAP-007] - China Extension Study

NCT ID: NCT04676412

Last Updated: 2025-04-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

107 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-10-23

Study Completion Date

2024-03-29

Brief Summary

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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).

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Detailed Description

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The main study will have a duration of approximately 5 years and the extension period will have a duration of approximately 1 year. The base study and the China extension to MK-7902-007 (NCT03829332) will enroll a total of approximately 120 Chinese participants.

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.

Conditions

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Non-small Cell Lung Cancer

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Lenvatinib

Intervention Type DRUG

oral capsule

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.

Group Type ACTIVE_COMPARATOR

Pembrolizumab

Intervention Type BIOLOGICAL

IV infusion

Placebo for lenvatinib

Intervention Type DRUG

oral capsule

Interventions

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Pembrolizumab

IV infusion

Intervention Type BIOLOGICAL

Lenvatinib

oral capsule

Intervention Type DRUG

Placebo for lenvatinib

oral capsule

Intervention Type DRUG

Other Intervention Names

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MK-3475 KEYTRUDA® MK-7902 E7080 LENVIMA®

Eligibility Criteria

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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 \[AJCC\])
* Has measurable disease based on Response Evaluation Criteria in Solid Tumors 1.1 (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 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 radiographic evidence of encasement or invasion of a major blood vessel, or of intratumoral cavitation
* 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 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eisai Inc.

INDUSTRY

Sponsor Role collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Anhui Provincial Hospital ( Site 0108)

Hefei, Anhui, China

Site Status

The First Affiliated Hospital of Anhui Medical University ( Site 0113)

Hefei, Anhui, China

Site Status

Peking Union Medical College Hospital ( Site 0105)

Beijing, Beijing Municipality, China

Site Status

Beijing Cancer Hospital ( Site 0102)

Beijing, Beijing Municipality, China

Site Status

Beijing Chest Hospital Capital Medical University ( Site 0111)

Beijing, Beijing Municipality, China

Site Status

Xiangya Hospital of Central South University ( Site 0115)

Changsha, Hunan, China

Site Status

Hunan Cancer Hospital ( Site 0104)

Changsha, Hunan, China

Site Status

Zhongshan Hospital Fudan University ( Site 0100)

Shanghai, Hunan, China

Site Status

Jiangsu Cancer Hospital ( Site 0101)

Nanjing, Jiangsu, China

Site Status

The First Hospital of Jilin University ( Site 0110)

Changchun, Jilin, China

Site Status

Shanghai Chest Hospital ( Site 0112)

Shanghai, Shanghai Municipality, China

Site Status

1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)

XiAn, Shanxi, China

Site Status

West China Hospital of Sichuan University ( Site 0117)

Chengdu, Sichuan, China

Site Status

The First Affiliated Hospital Zhejiang University ( Site 0106)

Hangzhou, Zhejiang, China

Site Status

Hangzhou First People's Hospital ( Site 0109)

Hangzhou, Zhejiang, China

Site Status

2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)

Hangzhou, Zhejiang, China

Site Status

Zhejiang Cancer Hospital ( Site 0116)

Hangzhou, Zhejiang, China

Site Status

Countries

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China

References

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Yang JC, Han B, De La Mora Jimenez E, Lee JS, Koralewski P, Karadurmus N, Sugawara S, Livi L, Basappa NS, Quantin X, Dudnik J, Ortiz DM, Mekhail T, Okpara CE, Dutcus C, Zimmer Z, Samkari A, Bhagwati N, Csoszi T. Pembrolizumab With or Without Lenvatinib for First-Line Metastatic NSCLC With Programmed Cell Death-Ligand 1 Tumor Proportion Score of at least 1% (LEAP-007): A Randomized, Double-Blind, Phase 3 Trial. J Thorac Oncol. 2024 Jun;19(6):941-953. doi: 10.1016/j.jtho.2023.12.023. Epub 2023 Dec 29.

Reference Type RESULT
PMID: 38159809 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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https://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

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MK-7902-007

Identifier Type: OTHER

Identifier Source: secondary_id

E7080-G000-314

Identifier Type: OTHER

Identifier Source: secondary_id

LEAP-007

Identifier Type: OTHER

Identifier Source: secondary_id

7902-007 China Extension

Identifier Type: -

Identifier Source: org_study_id

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