Phase 3
N=794
Safety and Efficacy of Lenvatinib (E7080/MK-7902) in Combination With Pembrolizumab (MK-3475) Versus Lenvatinib as First-line Therapy in Participants With Advanced Hepatocellular Carcinoma (MK-7902-002/E7080-G000-311/LEAP-002)
Carcinoma, Hepatocellular
Bottom Line
View on ClinicalTrials.gov: NCT03713593 ↗Enrolled (actual)
794
Serious AEs
43.5%
Results posted
Jul 2023
Primary outcome: Primary: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) — 8.2; 8.1 Months
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- lenvatinib (Drug); pembrolizumab (Biological); saline placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Jun 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
8.2; 8.1 | — |
| PRIMARY Overall Survival (OS) |
21.2; 19.0 | 0.0227 sig |
| SECONDARY Objective Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
26.1; 17.5 | — |
| SECONDARY Duration of Response (DOR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
4.1; 4.0 | — |
| SECONDARY Disease Control Rate (DCR) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
81.3; 78.4 | — |
| SECONDARY Time to Disease Progression (TTP) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) |
8.3; 8.2 | — |
| SECONDARY Progression-free Survival (PFS) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
8.4; 8.1 | — |
| SECONDARY Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
40.8; 34.1 | — |
| SECONDARY Duration of Response (DOR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
2.1; 2.1 | — |
| SECONDARY Disease Control Rate (DCR) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
84.3; 83.2 | — |
| SECONDARY Time to Disease Progression (TTP) Per Modified Response Evaluation Criteria in Solid Tumors (mRECIST) |
10.4; 8.3 | — |
| SECONDARY Number of Participants Who Experienced an Adverse Event (AE) |
394; 392 | — |
| SECONDARY Number of Participants Who Experienced an Serious Adverse Event (SAE) |
185; 159 | — |
| SECONDARY Number of Participants Who Experienced an Immune-related Adverse Event (irAE) of Clinical Interest |
210; 184 | — |
| SECONDARY Number of Participants Who Experienced an Hepatic Event of Clinical Interest (HECI) |
71; 77 | — |
| SECONDARY Number of Participants Who Discontinued Study Drug Due to an Adverse Event |
51; 41 | — |
Summary
The purpose of this study is to evaluate the safety and efficacy of lenvatinib (E7080/MK-7902) in combination with pembrolizumab (MK-3745) versus lenvatinib in combination with placebo as first-line therapy for the treatment of advanced hepatocellular carcinoma in adult participants.
The primary hypotheses of this study are that lenvatinib plus pembrolizumab is superior to lenvatinib plus placebo with respect to progression-free survival (PFS) and overall survival (OS).
Eligibility Criteria
Inclusion Criteria
- Is male or female and ≥18 years of age at the time of signing the informed consent
- Has a diagnosis of hepatocellular carcinoma confirmed by radiology, histology, or cytology
- Has Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
- Has a Child-Pugh class A liver score
- Has a predicted life expectancy of >3 months
- Has at least one measurable hepatocellular carcinoma (HCC) lesion based on RECIST 1.1 as confirmed by BICR
- Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1
- Participants with hepatitis B will be eligible as long as their virus is well controlled
Exclusion Criteria
- Has had esophageal or gastric variceal bleeding within the last 6 months
- Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib
- Has a preexisting Grade ≥3 gastrointestinal or non-gastrointestinal fistula
- Has clinically significant hemoptysis from any source or tumor bleeding within 2 weeks prior to the first dose of study intervention
- Has significant cardiovascular impairment within 12 months of the first dose of study intervention such as history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or cerebrovascular accident stroke, or cardiac arrhythmia associated with hemodynamic instability
- Has had major surgery to the liver within 4 weeks prior to the first dose of study intervention
- Has had a minor surgery (ie, simple excision) within 7 days prior to the first dose of study intervention
- Has serious non-healing wound, ulcer, or bone fracture
- Has received any systemic chemotherapy for HCC or chemotherapy for any malignancy in the past 3 years
- Has received prior therapy with an anti-programmed cell death 1 (ant-PD-1), anti-programmed cell death ligand 1 (anti-PD-L1), or anti- programmed cell death ligand 2 (anti-PD-L2) agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX-40, or CD137)
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior the first dose of study intervention
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years with the exceptions of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that has undergone potentially curative therapy
- Has a known history of, or any evidence of, central nervous system (CNS) metastases and/or carcinomatous meningitis as assessed by local site investigator
- Has severe hypersensitivity (≥Grade 3) to study intervention and/or any of their excipients
- Has an active autoimmune disease that has required systemic treatment in past 2 years
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- Has urine protein ≥1 grams/24 hours
- Prolongation of corrected QT (QTc) interval to >480 milliseconds (corrected by Fridericia Formula)
- Has left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO)
- Has an active infection requiring systemic therapy with the exceptions of hepatitis B virus (HBV) or hepatitis C virus (HCV)
- Has a known history of human immunodeficiency virus (HIV) infection
- Has known active tuberculosis (Bacillus tuberculosis)
- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the stud
Data sourced from ClinicalTrials.gov (NCT03713593). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.