A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma

NCT ID: NCT03006926

Last Updated: 2023-12-13

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-13

Study Completion Date

2022-11-22

Brief Summary

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This is an open-label Phase 1b study designed to evaluate the tolerability and safety of lenvatinib in combination with pembrolizumab in participants with hepatocellular carcinoma (HCC). The study will evaluate objective response rate and duration of response by modified Response Evaluation Criteria In Solid Tumors (mRECIST) for HCC and Response Evaluation Criteria In Solid Tumors (RECIST 1.1) based on independent imaging review (IIR).

Detailed Description

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Conditions

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Hepatocellular Carcinoma

Keywords

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hepatocellular carcinoma E7080 lenvatinib pembrolizumab Japan

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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lenvatinib 8 or 12 mg plus pembrolizumab 200 mg

Participants will receive oral lenvatinib at a starting dose of 8 or 12 milligrams (mg) once a day (QD) in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W) on a 21-day treatment cycle. The starting dose of lenvatinib will be based on Baseline body weight. Participants weighing greater than or equal to 60 kilograms (kg) will receive 12 mg QD; participants weighing less than 60 kg will receive 8 mg QD.

Group Type EXPERIMENTAL

lenvatinib

Intervention Type DRUG

4 mg capsules

pembrolizumab (200 mg)

Intervention Type DRUG

30-minute intravenous infusion

Interventions

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lenvatinib

4 mg capsules

Intervention Type DRUG

pembrolizumab (200 mg)

30-minute intravenous infusion

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Confirmed diagnosis of hepatocellular carcinoma (HCC)
* HCC for which no other appropriate therapy is available. Note: Expansion Part: No prior systemic therapy for advanced/unresectable HCC
* Stage B (not applicable for transarterial chemoembolization \[TACE\]), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
* At least 1 measurable target lesion according to modified Response Evaluation Criteria in Solid Tumors (mRECIST)
* Child-Pugh score A
* Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
* Total triiodothyronine (T3) or free T3 and free thyroxine (T4) are within normal limits. (control by thyroid replacement therapy is acceptable.) Participants with T3, free T3 or free T4 abnormalities at screening who are asymptomatic can be eligible
* Adequately controlled blood pressure
* Adequate renal function
* Adequate bone marrow function
* Adequate blood coagulation function
* Adequate liver function
* Males or females age ≥ 18 years at the time of informed consent
* Voluntary agreement to provide written informed consent and the willingness and ability to comply with all aspects of the protocol

Exclusion Criteria

* Prior treatment with lenvatinib or any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
* Active malignancy (except for HCC or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 36 months
* Any medical or other condition which, in the opinion of the investigator, would preclude participation in a clinical trial
* Active infection (any infection requiring systemic treatment). Hepatitis B or C \[HBV/HCV\] is allowed
* Participants with CNS metastases are not eligible, unless they have completed local therapy (eg, whole brain radiation therapy \[WBRT\], surgery or radiosurgery) and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (eg, radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Eisai Co., Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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California Pacific Medical Center (CPMC)

San Francisco, California, United States

Site Status

Ronald Reagan UCLA Medical Center

Santa Monica, California, United States

Site Status

Mercy Medical Center

Baltimore, Maryland, United States

Site Status

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status

Icahn School of Medicine Mount Sinai

New York, New York, United States

Site Status

BRCR Global Texas

Edinburg, Texas, United States

Site Status

Hôpital Haut-Levêque Centre médico-chirurgical Magellan

Pessac, Bordeaux, France

Site Status

Centre Eugène Marquis de Rennes

Rennes, Brittany Region, France

Site Status

CHU Toulouse

Toulouse, Occitanie, France

Site Status

Hôpital Timone

Marseille, Provence-Alpes-Côte d'Azur Region, France

Site Status

IRCCS Istituto Clinico Humanitas

Milan, Lombardy, Italy

Site Status

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

Bologna, Province of Bologna, Italy

Site Status

Eisai Trial Site 2

Kashiwa, Chiba, Japan

Site Status

Eisai Trial Site 4

Kawasaki, Kanagawa, Japan

Site Status

Eisai Trial Site 3

Sayama, Osaka, Japan

Site Status

Eisai Trial Site 1

Chuo-ku, Tokyo, Japan

Site Status

Republican Clinical Oncology Dispensary

Ufa, Bashkortostan Republic, Russia

Site Status

St. Petersburg City Clinical Oncology Dispansery

Saint Petersburg, Leningradskaya Oblast', Russia

Site Status

S.I. Russian Oncological Research Center n.a. N. N. Blokhin RAMS

Moscow, Moscow Oblast, Russia

Site Status

Altay Regional Oncology Dispensary

Barnaul, , Russia

Site Status

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

Site Status

Hospital General Universitario Gregorio Marañón

Madrid, Madrid, Spain

Site Status

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Site Status

Hospital Infanta Cristina de Badajoz

Badajoz, Province of Badajoz, Spain

Site Status

Hospital Universitario de Salamanca

Salamanca, Province of Salamanca, Spain

Site Status

Royal Free Hospital

London, Greater London, United Kingdom

Site Status

Countries

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Germany United States France Italy Japan Russia Spain United Kingdom

References

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Finn RS, Ikeda M, Zhu AX, Sung MW, Baron AD, Kudo M, Okusaka T, Kobayashi M, Kumada H, Kaneko S, Pracht M, Mamontov K, Meyer T, Kubota T, Dutcus CE, Saito K, Siegel AB, Dubrovsky L, Mody K, Llovet JM. Phase Ib Study of Lenvatinib Plus Pembrolizumab in Patients With Unresectable Hepatocellular Carcinoma. J Clin Oncol. 2020 Sep 10;38(26):2960-2970. doi: 10.1200/JCO.20.00808. Epub 2020 Jul 27.

Reference Type DERIVED
PMID: 32716739 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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KEYNOTE 524

Identifier Type: OTHER

Identifier Source: secondary_id

2018-000522-55

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

E7080-J081-116

Identifier Type: -

Identifier Source: org_study_id