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

Non-small Cell Lung Cancer Clinical Trial

— 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 Nonsmall Cell Lung Cancer (NSCLC) Whose Tumors Have a Tumor Proportion Score (TPS) Greater Than or Equal to 1% (LEAP-007)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04676412
• Other study ID #: 7902-007 China Extension
• Secondary ID: MK-7902-007E7080
• Status: Completed
• Phase: Phase 3
• Start date: October 23, 2019
• Est. completion date: March 29, 2024

Study information

• Verified date: May 2024
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: March 29, 2024
• Est. primary completion date: May 19, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Biological:
• Pembrolizumab
IV infusion

Drug:
• Lenvatinib
oral capsule
• Placebo for lenvatinib
oral capsule

Locations

Country	Name	City	State
China	Beijing Cancer Hospital ( Site 0102)	Beijing	Beijing
China	Beijing Chest Hospital Capital Medical University ( Site 0111)	Beijing	Beijing
China	Peking Union Medical College Hospital ( Site 0105)	Beijing	Beijing
China	The First Hospital of Jilin University ( Site 0110)	Chang chun	Jilin
China	Hunan Cancer Hospital ( Site 0104)	Changsha	Hunan
China	Xiangya Hospital of Central South University ( Site 0115)	Changsha	Hunan
China	West China Hospital of Sichuan University ( Site 0117)	Chengdu	Sichuan
China	2nd Affil Hosp of Zhejiang University College of Medicine ( Site 0114)	Hangzhou	Zhejiang
China	Hangzhou First People's Hospital ( Site 0109)	Hangzhou	Zhejiang
China	The First Affiliated Hospital Zhejiang University ( Site 0106)	Hangzhou	Zhejiang
China	Zhejiang Cancer Hospital ( Site 0116)	Hangzhou	Zhejiang
China	Anhui Provincial Hospital ( Site 0108)	Hefei	Anhui
China	The First Affiliated Hospital of Anhui Medical University ( Site 0113)	Hefei	Anhui
China	Jiangsu Cancer Hospital ( Site 0101)	Nanjing	Jiangsu
China	Shanghai Chest Hospital ( Site 0112)	Shanghai	Shanghai
China	Zhongshan Hospital Fudan University ( Site 0100)	Shanghai	Hunan
China	1st Affil Hosp of Med College of Xi'an Jiaotong University ( Site 0103)	XiAn	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC	Eisai Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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. Note: The appearance of one or more new lesions was also considered PD. Data were from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by BICR per RECIST 1.1 was presented.	Up to approximately 18 months
Primary	Overall Survival (OS)	OS was defined as the time from date of randomization to date of death from any cause.	Up to approximately 18 months
Secondary	Objective Response Rate (ORR) Per RECIST 1.1 as Assessed by BICR	ORR was defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. The percentage of participants who experienced CR or PR as assessed by BICR were presented.	Up to approximately 18 months
Secondary	Number of Participants Who Experience an Adverse Event (AE)	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.	Up to approximately 27 months
Secondary	Number of Participants Who Discontinue Study Treatment Due to an AE	The number of participants who discontinue study treatment due to an AE will be presented.	Up to approximately 24 months
Secondary	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	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.	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)
Secondary	Change From Baseline in Quality of Life (QoL)(EORTC QLQ-C30 Item 30) Score	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.	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)
Secondary	Change From Baseline in Cough (EORTC Quality of Life Questionnaire-Lung Cancer Module 13 [QLQ-LC13] Item 31) Score	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.	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)
Secondary	Change From Baseline in Chest Pain (EORTC QLQ-LC13 Item 40) Score	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.	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)
Secondary	Change From Baseline in Dyspnea (EORTC QLQ-C30 Item 8) Score	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.	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)
Secondary	Change From Baseline in Physical Functioning (EORTC QLQ-C30 Items 1-5) Score	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.	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)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in Global Health Status (GHS)(EORTC QLQ-C30 Item 29) Score	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.	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)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in Quality of Life (QoL)(EORTC QLQ-C30 Item 30) Score	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.	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)
Secondary	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)	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.	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)
Secondary	Time to True Deterioration (TTD) Based on Change From Baseline in EORTC QLQ-C30 Physical Functioning (Items 1-5) Score	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.	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)

External Links

•   Merck Clinical Trials Information