Safety and Efficacy Study of Pemetrexed + Platinum Chemotherapy + Pembrolizumab (MK-3475) With or Without Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Metastatic Nonsquamous Non-small Cell Lung Cancer (MK-7902-006/E7080-G000-315/LEAP-006)-China Extension Study

NCT04716933 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: 7902-006 China ExtensionMK-7902-006E7080-G000-315LEAP-006
• Study Type: interventional
• Target: 201
• Locations: 1 country
• Sites: 19

Brief Summary

The purpose of this study is to assess the safety and efficacy of pemetrexed+platinum chemotherapy+pembrolizumab (MK-3475) with or without lenvatinib (MK-7902/E7080) as first-line intervention in adults from mainland China with metastatic nonsquamous non-small cell lung cancer. The primary study hypotheses state that: 1) the combination of lenvatinib+platinum doublet chemotherapy+pembrolizumab prolongs Progression-free Survival (PFS) as assessed by blinded independent central review (BICR) per modified Response Evaluation Criteria in Solid Tumors version 1.1 (RESIST 1.1) compared to matching placebo+platinum doublet chemotherapy+pembrolizumab, and 2) the combination of lenvatinib+platinum doublet chemotherapy+pembrolizumab prolongs Overall Survival (OS) compared to matching placebo+platinum doublet chemotherapy + pembrolizumab.

Conditions

Nonsquamous 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)

Outcome Measures

Primary Outcomes (2)

• Part 2: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  PFS is 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 is 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 are from the product-limit (Kaplan-Meier) method for censored data. PFS as assessed by blinded independent central review (BICR) per RECIST 1.1 is presented.

  Up to approximately 43 months

• Part 2: Overall Survival (OS)

  OS is defined as the time from randomization to the time of death from any cause. OS is presented.

  Up to approximately 43 months

Secondary Outcomes (4)

• Part 2: Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 57 months

• Part 2: Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)

  Up to approximately 57 months

• Part 2: Number of Participants Who Experienced an Adverse Event (AE)

  Up to approximately 42 months

• Part 2: Number of Participants Who Discontinued Study Drug Due to an Adverse Event

  Up to approximately 42 months

Study Arms (2)

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib

EXPERIMENTAL

Participants receive carboplatin Area Under Curve 5 mg/mL/min (AUC5) or cisplatin 75 mg/m\^2 via intravenous (IV) infusion on Day 1 of each 3-week cycle (Q3W) for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS lenvatinib via oral capsule once daily.

Biological: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Lenvatinib

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

PLACEBO COMPARATOR

Participants receive carboplatin AUC5 or cisplatin 75 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pemetrexed 500 mg/m\^2 via IV infusion Q3W for 4 cycles PLUS pembrolizumab via IV infusion Q3W for up to 35 cycles (up to 2 years) PLUS (Part 2 only) placebo matching lenvatinib via oral capsule once daily.

Biological: Pembrolizumab; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Placebo matching lenvatinib

Interventions

Pembrolizumab BIOLOGICAL

IV infusion Q3W

Also known as: MK-3475

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib; Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

Carboplatin DRUG

IV infusion Q3W

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib; Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

Cisplatin DRUG

IV infusion Q3W

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib; Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

Pemetrexed DRUG

IV infusion Q3W

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib; Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

Lenvatinib DRUG

Oral capsule once daily

Also known as: MK-7902, E7080

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Lenvatinib

Placebo matching lenvatinib DRUG

Oral capsule once daily

Pemetrexed+Platinum Chemotherapy+Pembrolizumab+Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of Stage IV (American Joint Committee on Cancer \[AJCC\], version 8 or current version) nonsquamous NSCLC.
• Confirmation that Epidermal Growth Factor Receptor (EGFR), ALK Receptor Tyrosine Kinase (ALK), or ROS1 Receptor Tyrosine Kinase (ROS1)-directed therapy is not indicated as primary treatment (documentation of absence of tumor-activating EGFR mutations AND absence of ALK and ROS1 gene rearrangements OR presence of a Kirsten Rat Sarcoma (KRAS) gene mutation).
• Have measurable disease based on RECIST 1.1. Note: Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable (eligible for selection as target lesions) if they have shown documented growth since the completion of radiation.
• Provided an evaluable archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion (that was not previously irradiated) for central PD-L1 testing.
• Life expectancy of at least 3 months.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the first dose of study intervention but before randomization.
• Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab and/or lenvatinib/matching placebo and up to 180 days after the last dose of chemotherapeutic agents. A male participant must also agree to the following: 1) abstinence from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent, OR 2) agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant, unless confirmed to be azoospermic (vasectomized or secondary to medical cause). Note: Men with a pregnant or breastfeeding partner must agree to remain abstinent from penile-vaginal intercourse or use a male condom during each episode of penile-vaginal penetration.
• Female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) not a WOCBP OR 2) a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis), during the intervention period and for at least 120 days after the last dose of study intervention.
• Adequate organ function.
• 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 prior to randomization. Note: Participants must not have a history of uncontrolled or poorly-controlled hypertension, defined as \>150/90 mm Hg for \>4 weeks despite standard medical management.

You may not qualify if:

• Known untreated central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, clinically stable, and have not required steroids for at least 14 days prior to the first dose of study intervention.
• History of (noninfectious) pneumonitis that required systemic steroids or current pneumonitis/interstitial lung disease.
• Radiographic evidence of major blood vessel invasion/infiltration.
• Known history of an additional malignancy, except if the participant has undergone potentially curative therapy with no evidence of that disease recurrence for at least 3 years since initiation of that therapy. Note: The time requirement also 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.
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention.
• Has had allogeneic tissue/solid organ transplant.
• Known history of human immunodeficiency virus (HIV) infection. HIV testing is not required unless mandated by the local health authority.
• Known history of Hepatitis B or active Hepatitis C. No testing for Hepatitis B or Hepatitis C is required unless mandated by the local health authority.
• History of a gastrointestinal condition or procedure that in the opinion of the investigator may affect oral drug absorption.
• Active hemoptysis (at least 0.5 teaspoon of bright red blood) within 2 weeks prior to the first dose of study intervention.
• Significant cardiovascular impairment within 12 months prior to the first dose of study intervention, including history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA)/stroke, or cardiac arrhythmia associated with hemodynamic instability.
• Known history of active tuberculosis.
• Active infection requiring systemic therapy.
• Has not recovered adequately from any toxicity and/or complication from major surgery prior to the first dose of study intervention.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead
• Eisai Inc.: collaborator

Study Sites (19)

Peking Union Medical College Hospital ( Site 0108)

Beijing, Beijing Municipality, 100006, China

Location

Cancer Hospital Chinese Academy of Medical Science ( Site 0117)

Beijing, Beijing Municipality, 100021, China

Location

Beijing Cancer Hospital ( Site 0120)

Beijing, Beijing Municipality, 100036, China

Location

The Second Hospital Affiliated to AMU ( Site 0119)

Chongqing, Chongqing Municipality, 400037, China

Location

First Affiliated Hospital of The Third Military Medical University ( Site 0118)

Chongqing, Chongqing Municipality, 400038, China

Location

Fujian Provincial Cancer Hospital ( Site 0102)

Fuzhou, Fujian, 350014, China

Location

Southern Medical University Nanfang Hospital ( Site 0121)

Guangzhou, Guangdong, 510515, China

Location

The Third Affiliated Hospital of Harbin Medical University ( Site 0100)

Harbin, Heilongjiang, 150081, China

Location

Henan Cancer Hospital ( Site 0112)

Zhengzhou, Henan, 450008, China

Location

Wuhan Union Hospital ( Site 0123)

Wuhan, Hubei, 430022, China

Location

Hubei Cancer Hospital ( Site 0122)

Wuhan, Hubei, 430079, China

Location

Zhongshan Hospital Fudan University ( Site 0103)

Shanghai, Hunan, 200032, China

Location

Jilin Cancer Hospital ( Site 0115)

Changchun, Jilin, 130103, China

Location

Shanghai Pulmonary Hospital ( Site 0101)

Shanghai, Shanghai Municipality, 200443, China

Location

Tianjin Medical University Cancer Institute & Hospital ( Site 0111)

Tianjin, Tianjin Municipality, 300060, China

Location

Cancer Hospital Affiliated to Xinjiang Medical University ( Site 0110)

Urumuqi, Xinjiang, 830000, China

Location

The First Affiliated Hospital Zhejiang University ( Site 0109)

Hangzhou, Zhejiang, 310003, China

Location

Zhejiang Cancer Hospital ( Site 0113)

Hangzhou, Zhejiang, 310022, China

Location

The First Affiliated Hospital of Wenzhou Medical University ( Site 0124)

Wenzhou, Zhejiang, 325000, China

Location

Related Links

• Merck Clinical Trials Information

MeSH Terms

Conditions

Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; Carboplatin; Cisplatin; Pemetrexed; lenvatinib

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 19, 2021
• First Posted: January 20, 2021
• Study Start: November 5, 2019
• Primary Completion: August 11, 2023
• Study Completion: August 30, 2024
• Last Updated: September 9, 2025
• Results First Posted: October 4, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share

Locations

CN (19)