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A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma

Primary Purpose

Hepatocellular Carcinoma

Status

Completed

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

lenvatinib

pembrolizumab (200 mg)

About this trial

This is an interventional treatment trial for Hepatocellular Carcinoma focused on measuring hepatocellular carcinoma, E7080, lenvatinib, pembrolizumab, Japan

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

California Pacific Medical Center (CPMC)
Ronald Reagan UCLA Medical Center
Mercy Medical Center
Massachusetts General Hospital
Icahn School of Medicine Mount Sinai
BRCR Global Texas
Hôpital Haut-Levêque Centre médico-chirurgical Magellan
Centre Eugène Marquis de Rennes
CHU Toulouse
Hôpital Timone
IRCCS Istituto Clinico Humanitas
Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi
Eisai Trial Site 2
Eisai Trial Site 4
Eisai Trial Site 3
Eisai Trial Site 1
Republican Clinical Oncology Dispensary
St. Petersburg City Clinical Oncology Dispansery
S.I. Russian Oncological Research Center n.a. N. N. Blokhin RAMS
Altay Regional Oncology Dispensary
Hospital Universitario Marqués de Valdecilla
Hospital General Universitario Gregorio Marañón
Hospital Universitario 12 de Octubre
Hospital Infanta Cristina de Badajoz
Hospital Universitario de Salamanca
Royal Free Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

lenvatinib 8 or 12 mg plus pembrolizumab 200 mg

Arm Description

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.

Outcomes

Primary Outcome Measures

DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs)

DLT was graded according to Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03). DLT was defined as any of the following: (1) any of the hematological or nonhematological toxicities considered to be at least possibly related to lenvatinib and/or pembrolizumab occurring during Cycle 1; (2) failure to >=75 percent (%) of the planned dosage of lenvatinib as a result of treatment-related toxicity during Cycle 1; (3) participants who discontinue treatment due to treatment-related toxicity in Cycle 1; (4) >2 week delay in starting pembrolizumab in Cycle 2 because of a treatment-related toxicity, even if the toxicity does not meet DLT criteria.

DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1 Assessed by Independent Imaging Review (IIR)

ORR was defined as the percentage of participants who had best overall response (BOR) of complete response (CR) or partial response (PR) based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by IIR analysis. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 millimeter [mm] if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the long diameter (LD) (hereafter referred to as sum of LD) of all target lesions, as compared with Baseline summed LD.

DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR

DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on mRECIST assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

DLT+Expansion Part: Duration of Response (DOR) Based on RECIST 1.1 Assessed by IIR

DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

Secondary Outcome Measures

DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review

ORR was defined as the percentage of participants who had BOR of CR or PR based on mRECIST assessed by investigator review. Responses (PR or CR) were confirmed no less than 4 weeks after the initial response. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.

DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review

DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) based on mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review

PFS was defined as the time from the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) based on mRECIST and RECIST 1.1 assessed by IIR, and mRECIST assessed by investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

DLT+Expansion Part: Time-to Progression (TTP) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review

TTP was defined as the time from the first study dose date to the date of first documentation of PD, based on mRECIST and RECIST 1.1 assessed by IIR and mRECIST assessed by an investigator review. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by IIR

TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.

DLT+Expansion Part: Time-to Response (TTR) Based on RECIST 1.1 Assessed by IIR

TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to RECIST 1.1 assessed by IIR. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.

DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by Investigator Review

TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.

DLT+Expansion Part: Overall Survival (OS)

OS was measured from the date of first dose of study drug until date of death from any cause. Participants who were lost to follow-up and the participants who were alive at the date of data cutoff was censored at the date the participant was last known alive, whichever came earlier.

Cmax: Maximum Observed Plasma Concentration for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Tmax: Time to Reach the Cmax for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

AUC(0-ti): Area Under The Plasma Concentration-time Curve From Zero (Pre-Dose) to a Given Sampling Time (ti) for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

t1/2: Terminal Elimination Phase Half-Life for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

CL/F: Apparent Total Clearance for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Vz/F: Apparent Volume of Distribution at Terminal Phase for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Tss,Max: Time to Maximum Concentration at Steady State For Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Clss/F: Apparent Total Clearance Following Oral Administration at Steady State for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Css,Av: Average Steady State Plasma Concentration for Lenvatinib and Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Rac (Cmax): Accumulation Index of Cmax for Lenvatinib and Pembrolizumab

Rac (Cmax) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Rac (AUC): Accumulation Index of AUC for Lenvatinib and Pembrolizumab

Rac (AUC) was calculated as the ratio of drug concentrations observed during a dosing interval at steady state divided by drug concentrations seen during the dosing interval after a single (first) dose. Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Full Information

NCT ID

NCT03006926

First Posted

December 27, 2016

Last Updated

January 13, 2023

Sponsor

Eisai Co., Ltd.

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT03006926

Brief Title

A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma

Official Title

An Open-Label Phase 1b Trial of Lenvatinib Plus Pembrolizumab in Subjects With Hepatocellular Carcinoma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2022

Overall Recruitment Status

Completed

Study Start Date

February 13, 2017 (Actual)

Primary Completion Date

October 31, 2019 (Actual)

Study Completion Date

November 22, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Eisai Co., Ltd.

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hepatocellular Carcinoma

Keywords

hepatocellular carcinoma, E7080, lenvatinib, pembrolizumab, Japan

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

104 (Actual)

8. Arms, Groups, and Interventions

Arm Title

lenvatinib 8 or 12 mg plus pembrolizumab 200 mg

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

lenvatinib

Intervention Description

4 mg capsules

Intervention Type

Drug

Intervention Name(s)

pembrolizumab (200 mg)

Intervention Description

30-minute intravenous infusion

Primary Outcome Measure Information:

Title

DLT Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame

From first dose until 30 days after the last dose (up to approximately 2 years 9 months)

Title

Expansion Part: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame

From first dose until 30 days after the last dose (up to approximately 2 years 9 months)

Title

DLT Part: Number of Participants With Dose Limiting Toxicities (DLTs)

Description

Time Frame

From first dose of study drug up to Cycle 1 Day 21 (Cycle length= 21 days)

Title

DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST and RECIST 1.1 Assessed by Independent Imaging Review (IIR)

Description

Time Frame

From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)

Title

DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by IIR

Description

Time Frame

From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)

Title

DLT+Expansion Part: Duration of Response (DOR) Based on RECIST 1.1 Assessed by IIR

Description

DOR was defined as the time from the first documentation of CR or PR to the date of first documentation of PD or death (whichever occurred first) in participants with confirmed CR or PR based on RECIST 1.1 assessed by IIR analysis. CR defined as disappearance of all target lesions and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD. PD was defined as at least a 20% increase in the sum of LD of target and non-target lesions as compared with the smallest sum of LD and the increase of LD was at least 5 mm (including new lesions).

Time Frame

From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)

Secondary Outcome Measure Information:

Title

DLT+Expansion Part: Objective Response Rate (ORR) Based on mRECIST Assessed by Investigator Review

Description

Time Frame

From the first dose of study drug to the first date of documentation of disease progression or death whichever occurred first (up to approximately 2 years and 9 months)

Title

DLT+Expansion Part: Duration of Response (DOR) Based on mRECIST Assessed by Investigator Review

Description

Time Frame

From date of first documented confirmed CR or PR until date of first documentation of PD or death whichever occurred first (up to approximately 2 years and 9 months)

Title

DLT+Expansion Part: Progression-free Survival (PFS) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review

Description

Time Frame

From the first study dose date to the date of first documentation of disease progression or death (whichever occurred first) (up to approximately 2 years 9 months)

Title

DLT+Expansion Part: Time-to Progression (TTP) Based on mRECIST and RECIST 1.1 Assessed by IIR and Based on mRECIST Assessed by Investigator Review

Description

Time Frame

From date of first dose of study drug until disease progression (up to approximately 2 years 9 months)

Title

DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by IIR

Description

Time Frame

From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)

Title

DLT+Expansion Part: Time-to Response (TTR) Based on RECIST 1.1 Assessed by IIR

Description

Time Frame

From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)

Title

DLT+Expansion Part: Time-to Response (TTR) Based on mRECIST Assessed by Investigator Review

Description

TTR was defined as the time from the date of first study dose to the date of first documentation of CR or PR, in participants with confirmed CR or PR. It was evaluated according to mRECIST assessed by investigator review. CR defined as disappearance of all target and non-target lesions (a short diameter is <10 mm if it exists in a lymph node). PR defined as at least 30% decrease in the sum of the LD (hereafter referred to as sum of LD) of all target and non-target lesions, as compared with Baseline summed LD.

Time Frame

From date of first dose of study drug until CR or PR (up to approximately 2 years 9 months)

Title

DLT+Expansion Part: Overall Survival (OS)

Description

Time Frame

From the date of first dose of study drug until date of death from any cause (up to approximately 2 years 9 months)

Title

Cmax: Maximum Observed Plasma Concentration for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Tmax: Time to Reach the Cmax for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

AUC(0-ti): Area Under The Plasma Concentration-time Curve From Zero (Pre-Dose) to a Given Sampling Time (ti) for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

t1/2: Terminal Elimination Phase Half-Life for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

CL/F: Apparent Total Clearance for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Vz/F: Apparent Volume of Distribution at Terminal Phase for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Css,Max: Maximum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Css,Min: Minimum Observed Plasma Concentration at Steady State for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Tss,Max: Time to Maximum Concentration at Steady State For Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

AUC(0-tau): Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Clss/F: Apparent Total Clearance Following Oral Administration at Steady State for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Css,Av: Average Steady State Plasma Concentration for Lenvatinib and Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Rac (Cmax): Accumulation Index of Cmax for Lenvatinib and Pembrolizumab

Description

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Rac (AUC): Accumulation Index of AUC for Lenvatinib and Pembrolizumab

Description

Time Frame

Lenvatinib: Cycle 1 Days 1 and 15: 0-24 hours post-dose; Pembrolizumab: Cycles 1, 2, 4, 6, 8 Day 1: 0-24 hours post-infusion (each cycle length = 21 days)

Title

Number of Participants Positive for Serum Anti-drug Antibodies (ADA) Status for Pembrolizumab

Description

Data for this outcome measure will be reported after study completion (anticipated study completion date is November 2022).

Time Frame

Cycles 1 and 6 Day 1: Pre-dose (cycle length=21 days)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Facility Information:

Facility Name

California Pacific Medical Center (CPMC)

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

Ronald Reagan UCLA Medical Center

City

Santa Monica

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

Mercy Medical Center

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21202

Country

United States

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Icahn School of Medicine Mount Sinai

City

New York

State/Province

New York

ZIP/Postal Code

10029

Country

United States

Facility Name

BRCR Global Texas

City

Edinburg

State/Province

Texas

ZIP/Postal Code

78539

Country

United States

Facility Name

Hôpital Haut-Levêque Centre médico-chirurgical Magellan

City

Pessac

State/Province

Bordeaux

ZIP/Postal Code

33604

Country

France

Facility Name

Centre Eugène Marquis de Rennes

City

Rennes

State/Province

Brittany

ZIP/Postal Code

35042

Country

France

Facility Name

CHU Toulouse

City

Toulouse

State/Province

Occitanie

ZIP/Postal Code

31059

Country

France

Facility Name

Hôpital Timone

City

Marseille

State/Province

Provence-Alpes-Côte d'Azur

ZIP/Postal Code

13005

Country

France

Facility Name

IRCCS Istituto Clinico Humanitas

City

Milan

State/Province

Lombardy

ZIP/Postal Code

20089

Country

Italy

Facility Name

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi

City

Bologna

State/Province

Province Of Bologna

ZIP/Postal Code

15-40138

Country

Italy

Facility Name

Eisai Trial Site 2

City

Kashiwa

State/Province

Chiba

Country

Japan

Facility Name

Eisai Trial Site 4

City

Kawasaki

State/Province

Kanagawa

Country

Japan

Facility Name

Eisai Trial Site 3

City

Sayama

State/Province

Osaka

Country

Japan

Facility Name

Eisai Trial Site 1

City

Chuo-ku

State/Province

Tokyo

Country

Japan

Facility Name

Republican Clinical Oncology Dispensary

City

Ufa

State/Province

Bashkortostan

Country

Russian Federation

Facility Name

St. Petersburg City Clinical Oncology Dispansery

City

Saint Petersburg

State/Province

Leningrad Oblast

Country

Russian Federation

Facility Name

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

City

Moscow

State/Province

Moscow Oblast

Country

Russian Federation

Facility Name

Altay Regional Oncology Dispensary

City

Barnaul

Country

Russian Federation

Facility Name

Hospital Universitario Marqués de Valdecilla

City

Santander

State/Province

Cantabria

ZIP/Postal Code

39008

Country

Spain

Facility Name

Hospital General Universitario Gregorio Marañón

City

Madrid

State/Province

Community Of Madrid

ZIP/Postal Code

28007

Country

Spain

Facility Name

Hospital Universitario 12 de Octubre

City

Madrid

State/Province

Community Of Madrid

ZIP/Postal Code

28041

Country

Spain

Facility Name

Hospital Infanta Cristina de Badajoz

City

Badajoz

State/Province

Province Of Badajoz

ZIP/Postal Code

06080

Country

Spain

Facility Name

Hospital Universitario de Salamanca

City

Salamanca

State/Province

Province Of Salamanca

ZIP/Postal Code

37007

Country

Spain

Facility Name

Royal Free Hospital

City

London

State/Province

Greater London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

32716739

Citation

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.

Results Reference

derived

Learn more about this trial

A Trial of Lenvatinib Plus Pembrolizumab in Participants With Hepatocellular Carcinoma

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