Clinical trial NCT04676412: 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
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 Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: programmed cell death 1 (PD-1, PD1)
programmed cell death-ligand 1 (PD-L1, PDL1)
programmed cell death-ligand 2 (PD-L2, PDL2)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
Collaborators: name: Eisai Inc.
First posted: 2020-12-21
Enrollment: 107
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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: 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.

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 \[AJCC\])
* 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

Primary outcomes:
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR)
timeFrame: Up to approximately 18 months
measure: Overall Survival (OS)
timeFrame: Up to approximately 18 months
Secondary outcomes:
measure: Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR
timeFrame: Up to approximately 18 months
measure: Number of Participants Who Experienced an Adverse Event (AE)
timeFrame: Up to approximately 52 months
measure: Number of Participants Who Discontinued Study Treatment Due to an AE
timeFrame: Up to approximately 30 months
measure: Change From Baseline in European Organization for Research and Treatment (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) Combined Global Health Status / Quality of Life (Items 29 & 30) Scale Combined Score
timeFrame: Baseline and Week 21
measure: Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score
timeFrame: Baseline and Week 21
measure: Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score
timeFrame: Baseline and Week 21
measure: Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score
timeFrame: Baseline and Week 21
measure: Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score
timeFrame: Baseline and Week 21
measure: Time to True Deterioration (TTD) in EORTC QLQ-C30 Combined Global Health Status /Quality of Life (Items 29 & 30) Scale Combined Score
timeFrame: Up to approximately 25 months
measure: Time to True Deterioration (TTD) in EORTC QLQ-LC13 Cough (Item 31) Scale Score
timeFrame: Up to approximately 25 months
measure: Time to True Deterioration (TTD) in EORTC QLQ-LC13 Chest Pain (Item 40) Scale Score
timeFrame: Up to approximately 25 months
measure: Time to True Deterioration (TTD) in EORTC QLQ-C30 Dyspnea (Item 8) Scale Score
timeFrame: Up to approximately 25 months
measure: Time to True Deterioration (TTD) in the Composite Endpoint of EORTC QLQ-LC13 Cough (Item 31), EORTC QLQ-LC13 Chest Pain (Item 40), or EORTC QLQ-C30 Dyspnea (Item 8)
timeFrame: Up to approximately 25 months
measure: Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score
timeFrame: Up to approximately 25 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital ( Site 0108)
state: Anhui
city: Hefei
country: China
facility: The First Affiliated Hospital of Anhui Medical University ( Site 0113)
state: Anhui
city: Beijing
country: China
facility: Peking Union Medical College Hospital ( Site 0105)
state: Beijing
city: Beijing
country: China
facility: Beijing Cancer Hospital ( Site 0102)
state: Beijing
city: Beijing
country: China
facility: Beijing Chest Hospital Capital Medical University ( Site 0111)
state: Beijing
city: Changsha
country: China
facility: Xiangya Hospital of Central South University ( Site 0115)
state: Hunan
city: Changsha
country: China
facility: Hunan Cancer Hospital ( Site 0104)
state: Hunan
city: Shanghai
country: China
facility: Zhongshan Hospital Fudan University ( Site 0100)
state: Hunan
city: Nanjing
country: China
facility: Jiangsu Cancer Hospital ( Site 0101)
state: Jiangsu
city: Chang chun
country: China
facility: The First Hospital of Jilin University ( Site 0110)
state: Jilin
city: Shanghai
country: China
facility: Shanghai Chest Hospital ( Site 0112)
state: Shanghai
city: XiAn
country: China
facility: 1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital of Sichuan University ( Site 0117)
state: Sichuan
city: Hangzhou
country: China
facility: The First Affiliated Hospital Zhejiang University ( Site 0106)
state: Zhejiang
city: Hangzhou
country: China
facility: Hangzhou First People's Hospital ( Site 0109)
state: Zhejiang
city: Hangzhou
country: China
facility: 2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)
state: Zhejiang
city: Hangzhou
country: China
facility: Zhejiang Cancer Hospital ( Site 0116)
state: Zhejiang
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.