NCT04889118

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

Completed Phase 3 Results posted Last updated 23 December 2025

What this trial tests

Phase 3 trial testing Pembrolizumab in Malignant Melanoma in 131 participants. Completed in 1 November 2024.

Timeline

14 July 2020

Primary endpoint
18 January 2023

1 November 2024

Quick facts

Lead sponsor	Merck Sharp & Dohme LLC
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	131
Start date	14 July 2020
Primary completion	18 January 2023
Estimated completion	1 November 2024
Sites	11 locations across China

Drugs / interventions tested

• Pembrolizumab (pembrolizumab) — full drug profile →
• Lenvatinib (LENVATINIB) — full drug profile →
• Placebo for lenvatinib — full drug profile →

Conditions studied

• Malignant Melanoma — all drugs for Malignant Melanoma →

Sponsor

Merck Sharp & Dohme LLC — full company profile →

Who can join

18 and older, any sex, with Malignant Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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) Primary · Up to approximately 30 months

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.

Group	Value	95% CI
Pembrolizumab+Lenvatinib	6.1	4.1 – 8.1
Pembrolizumab+Placebo	2.0	2.0 – 2.1

Overall Survival (OS) Primary · Up to approximately 30 months

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

Group	Value	95% CI
Pembrolizumab+Lenvatinib	19.9	11.9 – 26.8
Pembrolizumab+Placebo	17.0	12.7 – 25.7

Objective Response Rate (ORR) as Assessed by BICR Per RECIST 1.1 Secondary · Up to approximately 30 months

ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1. 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.

Group	Value	95% CI
Pembrolizumab+Lenvatinib	26.6	16.3 – 39.1
Pembrolizumab+Placebo	16.4	8.5 – 27.5

Duration of Response (DOR) as Assessed by BICR Per RECIST 1.1 Secondary · Up to approximately 30 months

For participants who demonstrated CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions), DOR is defined as the date of the first documented evidence of CR or PR until 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 follo

Group	Value	95% CI
Pembrolizumab+Lenvatinib	13.7	4.2 – NA
Pembrolizumab+Placebo	NA	6.5 – NA

Number of Participants With Adverse Events (AEs) Secondary · Up to approximately 50 months

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.

Group	Value	95% CI
Pembrolizumab+Lenvatinib	64
Pembrolizumab+Placebo	67

Number of Participants Who Discontinue Study Treatment Due to Adverse Events (AEs) Secondary · Up to approximately 39 months

The number of participants who discontinue study treatment due to an AE will be presented.

Group	Value	95% CI
Pembrolizumab+Lenvatinib	10
Pembrolizumab+Placebo	3

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 51 months. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembrolizumab+Lenvatinib

Serious: 14/64 (22%)

Deaths: 49/64

Pembrolizumab + Placebo

Serious: 12/67 (18%)

Deaths: 47/67

Serious adverse events (27 terms)

Reaction	System	Pembrolizumab+Lenvatinib	Pembrolizumab + Placebo
Urinary tract infection	Infections and infestations	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Cardiac arrest	Cardiac disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Haemorrhoids	Gastrointestinal disorders	—	—
Pancreatitis	Gastrointestinal disorders	—	—
Cholecystitis	Hepatobiliary disorders	—	—
COVID-19 pneumonia	Infections and infestations	—	—
Gastroenteritis	Infections and infestations	—	—
Pneumonia	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Traumatic fracture	Injury, poisoning and procedural complications	—	—
Aspartate aminotransferase increased	Investigations	—	—
Lipase increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Diabetes mellitus	Metabolism and nutrition disorders	—	—
Myositis	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Paraneoplastic syndrome	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Cerebral infarction	Nervous system disorders	—	—
Immune-mediated encephalitis	Nervous system disorders	—	—
Renal failure	Renal and urinary disorders	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Immune-mediated lung disease	Respiratory, thoracic and mediastinal disorders	—	—
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	—	—

Other adverse events (73 terms — click to expand)

Reaction	System	Pembrolizumab+Lenvatinib	Pembrolizumab + Placebo
Hypothyroidism	Endocrine disorders	—	—
Proteinuria	Renal and urinary disorders	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—
Hypertension	Vascular disorders	—	—
Weight decreased	Investigations	—	—
Hypercholesterolaemia	Metabolism and nutrition disorders	—	—
Aspartate aminotransferase increased	Investigations	—	—
Blood lactate dehydrogenase increased	Investigations	—	—
Hyperglycaemia	Metabolism and nutrition disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Gamma-glutamyltransferase increased	Investigations	—	—
Hyperuricaemia	Metabolism and nutrition disorders	—	—
Alanine aminotransferase increased	Investigations	—	—
Hypoalbuminaemia	Metabolism and nutrition disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Palmar-plantar erythrodysaesthesia syndrome	Skin and subcutaneous tissue disorders	—	—
Blood bilirubin increased	Investigations	—	—
Lipase increased	Investigations	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Hyponatraemia	Metabolism and nutrition disorders	—	—
Blood creatine phosphokinase increased	Investigations	—	—
Platelet count decreased	Investigations	—	—
Urinary occult blood positive	Investigations	—	—
White blood cell count decreased	Investigations	—	—
White blood cells urine positive	Investigations	—	—
Hyperthyroidism	Endocrine disorders	—	—
C-reactive protein increased	Investigations	—	—
Neutrophil count decreased	Investigations	—	—
Hypocalcaemia	Metabolism and nutrition disorders	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Urinary tract infection	Infections and infestations	—	—
Blood thyroid stimulating hormone increased	Investigations	—	—
Blood urea increased	Investigations	—	—
Vomiting	Gastrointestinal disorders	—	—
Blood creatinine increased	Investigations	—	—
Blood glucose increased	Investigations	—	—
Serum amyloid A protein increased	Investigations	—	—
Toothache	Gastrointestinal disorders	—	—

Most-reported serious reactions: Urinary tract infection, Acute myocardial infarction, Cardiac arrest, Colitis, Haemorrhoids, Pancreatitis, Cholecystitis, COVID-19 pneumonia.

Data from ClinicalTrials.gov NCT04889118 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Targeting cytokine and chemokine signaling pathways for cancer therapy.
   Yi M, Li T, Niu M, Zhang H, et al · · 2024 · cited 264× · PMID 39034318 · DOI 10.1038/s41392-024-01868-3
2. Trial Watch: combination of tyrosine kinase inhibitors (TKIs) and immunotherapy.
   Petrazzuolo A, Maiuri MC, Zitvogel L, Kroemer G, et al · · 2022 · cited 23× · PMID 35655707 · DOI 10.1080/2162402x.2022.2077898
3. Diagnosis and Management of Dermatologic Adverse Events from Systemic Melanoma Therapies.
   Fay CJ, Jakuboski S, Mclellan B, Allais BS, et al · · 2023 · cited 4× · PMID 37395930 · DOI 10.1007/s40257-023-00790-8