A Study of Lenvatinib Plus Nivolumab in Participants With Hepatocellular Carcinoma

NCT03418922 | Completed Phase 1 Results

• 1 other identifier: E7080-J081-117
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 6

Brief Summary

The primary objective of this study is to evaluate the tolerability and safety of a combination of lenvatinib plus nivolumab in participants with hepatocellular carcinoma (HCC).

Conditions

Carcinoma, Hepatocellular

Outcome Measures

Primary Outcomes (8)

• Part 1: 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 hematological or non-hematological toxicities considered to be at least possibly related to lenvatinib and/or nivolumab occurring during Cycle 1: 1) Febrile neutropenia or Grade 4 neutropenia for \>7 days; 2) Grade 4 thrombocytopenia and Grade 3 thrombocytopenia with bleeding; 3) Grade 4 anemia; 4) Clinical deterioration manifested by drug-related hepatic decompensation; 5) \>=Grade 3 non-hematological laboratory abnormalities with clinical symptoms that persisted; 6) Other Grade 3 toxicity lasting \>3 days or Grade 4 non-hematological toxicity of any duration; 7) Grade 2 uveitis, eye pain, or blurred vision that did not respond to topical therapy; 8) Failure to administer 8 or more dose of the planned administration number of study drug in Cycle 1 as a result of treatment-related toxicity.

  Cycle 1 (Cycle length = 28 days)

• Part 1 and Part 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

  A TEAE was defined as an adverse event (AE) that emerged during treatment and until the 30 days after the last dose or until the participants initiated new anticancer therapy, whichever was earlier, was absent at pretreatment (Baseline) or reemerged during treatment, was present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the AE was continuous. An SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening (that is, participant was at immediate risk of death from AE as it occurred; this did not include an event that, had it occurred in a more severe form or was allowed to continue, might have caused death), required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect (in the child of a participant who was exposed to the study drug).

  From the first dose of study drug until 30 days after the last dose (up to 53 months)

• Mean Change From Baseline in Vital Sign: Weight

  Mean change from baseline in weight were evaluated.

  Baseline, up to Month 53

• Mean Change From Baseline in Vital Sign: Body Mass Index

  Mean change from baseline in body mass index were evaluated.

  Baseline, up to Month 53

• Mean Change From Baseline in Vital Sign: SpO2 (Oxygen Saturation)

  Mean change from baseline in SpO2 were evaluated.

  Baseline, up to Month 53

• Number of Participants With Treatment-Emergent Markedly Abnormal Laboratory Values (TEMAVs)

  Treatment-emergent markedly abnormal laboratory value was defined as a postbaseline laboratory value with grade 3 or higher, and with a grade increase from baseline, (that is \[i.e.\] increasing grade 0 to 3 or higher, grade 1 to 3 or higher, grade 2 to 3 or higher, grade 3 to 4 or 5, grade 4 to 5). Test abnormalities were graded by Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 as Grade 1 =mild; Grade 2 =moderate; Grade 3/Grade 4 =severe/life-threatening, Grade 5 =death.

  From the first dose of study drug until 30 days after the last dose (up to 53 months)

• Number of Participants With Highest Post-Baseline Values for Eastern Cooperative Oncology Group Performance Status (ECOG-PS) Scale

  Performance status assessments were based on 5-grade ECOG scale (from 0 to 4), where 0=fully active, able to carry on all pre-disease performance without restriction; 1=restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (e.g., light house work, office work); 2=ambulatory and capable of all self-care but unable to carry out any work activities, up and about more than 50% of waking hours; 3=capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=completely disabled, cannot carry on any self-care, totally confined to bed or chair; 5=dead.

  Baseline, up to Month 53

• Change From Baseline in Left Ventricular Ejection Fraction (LVEF)

  Change from baseline in left ventricular ejection fraction (LVEF) were evaluated by multigated acquisition scan (MUGA) or echocardiogram.

  Baseline, up to Month 53

Secondary Outcomes (14)

• Part 1 and Part 2: Objective Response Rate (ORR) Based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) Assessed by Investigator Review

  From the first dose of study drug to the first date of documentation of PD or death, whichever occurred first (up to 52 months)

• Part 1, Cmax: Maximum Observed Plasma Concentration for Lenvatinib

  Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

• Part 1, Tmax: Time to Reach the Cmax for Lenvatinib

  Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

• Part 1, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to the Last Measurable Point for Lenvatinib

  Cycle 1 Day 1 and Day 15: 0-24 hours post-dose (Cycle length=28 days)

• Part 1, AUC(0-Inf): Area Under the Plasma Concentration-time Curve From Zero to Infinity for Lenvatinib

  Cycle 1 Day 1: 0-24 hours post-dose (Cycle length=28 days)

Study Arms (2)

Part 1: Lenvatinib Plus Nivolumab

EXPERIMENTAL

Participants will receive specified doses of lenvatinib (oral) and nivolumab (intravenous) on specified days.

Drug: Lenvatinib; Drug: Nivolumab

Part 2: Lenvatinib Plus Nivolumab

EXPERIMENTAL

If tolerable in Part 1, participants will receive specified doses of lenvatinib and nivolumab on specified days until criteria for discontinuation are met.

Drug: Lenvatinib; Drug: Nivolumab

Interventions

Lenvatinib DRUG

Specified doses will be administered orally on specified days.

Part 1: Lenvatinib Plus Nivolumab; Part 2: Lenvatinib Plus Nivolumab

Nivolumab DRUG

Specified doses will be administered intravenously on specified days.

Part 1: Lenvatinib Plus Nivolumab; Part 2: Lenvatinib Plus Nivolumab

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have confirmed diagnosis of hepatocellular carcinoma (HCC) with any of the following criteria:
• Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
• Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection
• Part 1: HCC for which no other appropriate therapy is available; Part 2: No prior systemic therapy for advanced/unresectable HCC
• Participants categorized to stage B (not applicable for transarterial chemoembolization), or stage C based on Barcelona Clinic Liver Cancer staging system
• Child-Pugh score A
• Participants must have an Eastern Cooperative Oncology Group Performance Status of 0 to 1
• Age greater than or equal to (\>=) 20 years at the time of informed consent

You may not qualify if:

• Active co-infection with hepatitis B and hepatitis C
• Participants with any active, known, or suspected autoimmune disease
• Participants being treated with drugs that strongly inhibit or induce CYP3A4 and that may be possibly used during this study
• Females who are breastfeeding or pregnant

Sponsors & Collaborators

• Eisai Co., Ltd.: lead
• Ono Pharmaceutical Co. Ltd: collaborator

Study Sites (6)

Eisai Trial Site 1

Kashiwa, Chiba, Japan

Location

Eisai Trial Site 6

Iizuka, Fukuoka, Japan

Location

Eisai Trial Site 3

Kawasaki, Kanagawa, Japan

Location

Eisai Trial Site 4

Sayama, Osaka, Japan

Location

Eisai Trial Site 2

Chuo-ku, Tokyo, Japan

Location

Eisai Trial Site 5

Chiba, Japan

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib; Nivolumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Eisai Inquiry Service
• Organization: Eisai Co., Ltd.

eisai-chiken_hotline@hhc.eisai.co.jp

none

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2018
• First Posted: February 1, 2018
• Study Start: January 16, 2018
• Primary Completion: December 28, 2022
• Study Completion: December 28, 2022
• Last Updated: June 20, 2024
• Results First Posted: June 20, 2024

Record last verified: 2022-05

Locations

JP (6)