Safety and Efficacy Study of Pembrolizumab (MK-3475) Combined With Lenvatinib (MK-7902/E7080) as First-line Intervention in Adults With Advanced Melanoma (MK-7902-003/E7080-G000-312/LEAP-003)-China Extension Study

NCT04889118 | Completed Phase 3 Results DMC

• 4 other identifiers: 7902-003 China ExtensionMK-7902-003E7080-G000-312LEAP-003
• Study Type: interventional
• Target: 131
• Locations: 1 country
• Sites: 11

Brief Summary

The purpose of the China Extension 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) as first-line treatment in Chinese participants with no prior systemic therapy for their advanced melanoma.

Conditions

Malignant Melanoma

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)

• Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review (BICR) Per Modified 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 occurs 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 is also considered PD. For this study, RECIST 1.1 has been modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ.

  Up to approximately 30 months

• Overall Survival (OS)

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

  Up to approximately 30 months

Secondary Outcomes (4)

• Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1

  Up to approximately 30 months

• Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1

  Up to approximately 30 months

• Number of Participants With Adverse Events (AEs)

  Up to approximately 50 months

• Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs)

  Up to approximately 39 months

Study Arms (2)

Pembrolizumab+Lenvatinib

EXPERIMENTAL

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 daily for up to at least 2 years.

Biological: Pembrolizumab; Drug: Lenvatinib

Pembrolizumab+Placebo

ACTIVE COMPARATOR

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 daily for up to at least 2 years.

Biological: Pembrolizumab; Drug: Placebo for lenvatinib

Interventions

Pembrolizumab BIOLOGICAL

IV infusion

Also known as: MK-3475, KEYTRUDA®

Pembrolizumab+Lenvatinib; Pembrolizumab+Placebo

Lenvatinib DRUG

Oral capsule

Also known as: MK-7902, E7080, LENVIMA®

Pembrolizumab+Lenvatinib

Placebo for lenvatinib DRUG

Oral capsule

Pembrolizumab+Placebo

Eligibility Criteria

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

You may qualify if:

• Has histologically or cytologically confirmed melanoma.
• Has unresectable Stage III or Stage IV melanoma, as per American Joint Committee on Cancer guidelines, not amenable to local therapy.
• Has been untreated for advanced or metastatic disease except as follows: a. proto-oncogene B-Raf (BRAF) V600 mutation-positive melanoma may have received standard of care targeted therapy as first-line therapy for advanced or metastatic disease. Participants that do not have a BRAF V600 mutation but did receive BRAF or BRAF/MEKi therapy are eligible to participate in this study after discussion with the medical monitor.
• b. Prior adjuvant or neoadjuvant therapy, with targeted therapy or immunotherapy (such as anti-cytotoxic T-lymphocyte-associated protein 4 \[CTLA-4\], anti-programmed cell death 1 \[anti-PD-1\] therapy or interferon) will only be permitted if relapse did not occur during active treatment or within 6 months of treatment discontinuation.
• Have documentation of BRAF V600-activating mutation status or consent to BRAF V600 mutation testing during the Screening period (participants with BRAF mutation-positive melanoma as well as BRAF wild-type or unknown are eligible).
• Has an Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Has the presence of ≥1 measurable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1.
• Provides a tumor biopsy. Participants must submit tumor sample during Screening for confirmation of adequacy of tumor tissue at a central pathology laboratory. Participants who do not submit a tumor tissue sample will not be randomized. The tumor biopsy may not be obtained from a lone target lesion. Confirmation of presence of tumor tissue is not required prior to randomization.
• Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). If participant received major surgery or radiation therapy of \>30 Gray (Gy), they must have recovered from the toxicity and/or complications from the intervention.
• Male participants must agree to use contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
• Female participants must not be pregnant, not breastfeeding, and ≥1 of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to use study-approved contraception during the treatment period and for at least 120 days after the last dose of study treatment.
• The participant (or legally acceptable representative) has provided documented informed consent for the study.
• Has adequately controlled blood pressure (BP) with or without antihypertensive medications, defined as BP ≤150/90 mmHg at screening and no change in antihypertensive medications within 1 week before Cycle 1 Day 1.

You may not qualify if:

• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment.
• Has a known additional malignancy that is progressing or requires active treatment.
• Exceptions include early stage cancers (carcinoma in situ or Stage 1, non-ulcerated primary melanoma \<1 mm in depth with no nodal involvement) treated with curative intent, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy.
• Has known active central nervous system metastases and/or carcinomatous meningitis.
• Has ocular melanoma.
• Has known hypersensitivity to active substances or any of their excipients including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody.
• Has an active autoimmune disease that has required systemic treatment in 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 not considered a form of systemic treatment.
• Has an active infection requiring systemic therapy.
• Has known history of human immunodeficiency virus (HIV) infection.
• Has known history of or is positive for hepatitis B virus or hepatitis C virus infection.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Has a history of active tuberculosis (Bacillus tuberculosis).
• Has presence of gastrointestinal condition including malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
• Has had a major surgery within 4 weeks prior to Cycle 1 Day 1. Adequate wound healing after major surgery must be assessed clinically and have resolved completely prior to Cycle 1 Day 1.
• Has a pre-existing Grade ≥3 gastrointestinal or non-gastrointestinal fistula.

Sponsors & Collaborators

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

Study Sites (11)

Beijing Cancer Hospital (0601)

Beijing, Beijing Municipality, 100036, China

Location

Fujian Provincial Cancer Hospital ( Site 0612)

Fuzhou, Fujian, 350014, China

Location

Sun Yat-Sen University Cancer Center (0602)

Guangzhou, Guangdong, 510000, China

Location

Henan Cancer Hospital ( Site 0610)

Zhengzhou, Henan, 450003, China

Location

Nanjing Drum Tower Hospital (0609)

Nanjing, Jiangsu, 210008, China

Location

The First Hospital Of Jilin University (0603)

Changchun, Jilin, 130021, China

Location

Fudan University Shanghai Cancer Center ( Site 0607)

Shanghai, Shanghai Municipality, 200032, China

Location

Tianjin Medical University Cancer Institute & Hospital (0606)

Tianjin, Tianjin Municipality, 300060, China

Location

Yunnan Cancer Hospital (0604)

Kunming, Yunnan, 430030, China

Location

Sir Run Run Shaw Hospital (0605)

Hangzhou, Zhejiang, 310018, China

Location

Zhejiang Cancer Hospital ( Site 0608)

Hangzhou, Zhejiang, 310022, China

Location

Related Links

• Merck Clinical Trial Information

MeSH Terms

Conditions

Melanoma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 12, 2021
• First Posted: May 17, 2021
• Study Start: July 14, 2020
• Primary Completion: January 18, 2023
• Study Completion: November 1, 2024
• Last Updated: December 23, 2025
• Results First Posted: July 9, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share

Locations

CN (11)