A Study of Lenvatinib Plus Nivolumab in Participants With Hepatocellular Carcinoma

Study Overview
=================
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).

Official Title
-----------------
A Phase 1b Trial of Lenvatinib Plus Nivolumab in Subjects With Hepatocellular Carcinoma

Conditions
-----------------
Carcinoma, Hepatocellular

Intervention / Treatment
-----------------
* Drug: Lenvatinib
* Drug: Nivolumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Lenvatinib Plus Nivolumab<br>Participants will receive specified doses of lenvatinib (oral) and nivolumab (intravenous) on specified days. | Drug: Lenvatinib<br>* Specified doses will be administered orally on specified days.<br>Drug: Nivolumab<br>* Specified doses will be administered intravenously on specified days.<br>|
| Experimental: Part 2: Lenvatinib Plus Nivolumab<br>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<br>* Specified doses will be administered orally on specified days.<br>Drug: Nivolumab<br>* Specified doses will be administered intravenously on specified days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants with Dose-Limiting Toxicities (DLTs) |  | Cycle 1 (28 days) | 
| Part 1 and Part 2: Number of Participants with Any Serious and/or Non-serious Adverse Event |  | From the date of screening until 30 days after the last dose (up to 41 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 and Part 2: Overall Response Rate (ORR) |  | From the date of screening until the last observation visit (up to 41 months) | 
| Part 1 and Part 2: Plasma Concentrations of Lenvatinib |  | Part 1, Cycle 1 Days 1 and 15: Pre-dose-24 hours, thereafter every Cycle Day 1 (Up to Cycle 24): Pre-dose; Part 2, Cycle 1 Day 1: 0.5-4 hours, Cycle 1 Day 15: Pre-dose-4 hours, Cycle 2, 4, 6 Day 1: Pre-dose (Cycle length is equal to [=] 28 days) | 
| Part 1 and Part 2: Serum Concentration of Nivolumab |  | Part 1 and Part 2, Cycle 1 and 5 Day 1: Pre-dose and Just before completion of administration, Cycles 1 and 5 Day 15, Cycle 2, 3, 4, 9, 13 Day 1: Pre-dose, thereafter every 4 cycles Day 1: Pre-dose (Cycle length=28 days) |