Toripalimab in Combination With Lenvatinib as Neoadjuvant Therapy in Resectable Hepatocellular Carcinoma

Study Overview
=================
Brief Summary
-----------------
This study will evaluate efficacy and safety of Toripalimab Injection (JS001) with or without Lenvatinib as a Neoadjuvant Therapy in patients with Resectable Hepatocellular Carcinoma (HCC)

Official Title
-----------------
A Phase Ib/II, Open-Label, Multi-Center Study Evaluating the Efficacy and Safety of Neoadjuvant Toripalimab Injection (JS001) or Toripalimab in Combination With Lenvatinib for Patients With Resectable Hepatocellular Carcinoma (HCC)

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

Intervention / Treatment
-----------------
* Drug: Toripalimab (JS001 )
* Drug: Toripalimab (JS001 ) Lenvatinib
* Drug: Toripalimab (JS001 ) Lenvatinib


Participation Criteria
=================
Eligibility Criteria
-----------------
Confirmed by histopathological or cytological examination; The criteria for resectability is met; Has at least one evaluable lesion according to the RECIST 1.1 standard and has not received local treatment; Exclusion Criteria: Patients who previously received anti-programmed death receptor-1 (PD-1) antibody, anti-programmed death ligand-1 (PD-L1) antibody, anti-programmed death ligand-2 (PD-L2) antibody or anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibodies, including those who have participated in a JS001 clinical study; Patients with a history of gastroesophageal varices or active cardia ulcers associated with a high risk of bleeding; Patients who have upper gastrointestinal hemorrhage within 1 year; Patients known to have fibrous layer HCC, sarcomatoid HCC or mixed cholangiocarcinoma and HCC; Other protocol defined inclusion/exclusion criteria could apply

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>During the neoadjuvant period, the patients will receive a single dose JS001 intravenous infusion of 480 mg. After the operation, the patients will receive JS001 240 mg Q3W for up to 48 weeks. | Drug: Toripalimab (JS001 )<br>* Given IV<br>|
| Experimental: Group B (Toripalimab, Lenvatinib)<br>During the neoadjuvant period, the patients will receive a single dose JS001 intravenous infusion of 480 mg in combination with oral lenvatinib at a starting dose of 8 or 12 mg once a day. After the operation, the patients will receive JS001 240 mg Q3W and lenvatinib for up to 48 weeks. | Drug: Toripalimab (JS001 ) Lenvatinib<br>* Given IV 4 mg capsules<br>|
| Active Comparator: Group C (Toripalimab, Lenvatinib)<br>During the neoadjuvant period, the patients will receive a single dose JS001 intravenous infusion of 480 mg in combination with oral lenvatinib at a starting dose of 8 or 12 mg once a day. After the operation, the patients will receive JS001 240 mg Q3W for up to 48 weeks. | Drug: Toripalimab (JS001 ) Lenvatinib<br>* Given IV 4 mg capsules<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological response rate | CPR，MPR | Up to 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | ORR is defined as the percentage of participants who achieved CR or PR | up to 2 months | 
| Percentage of R0 resection | Used for assessment of the feasibility of the neoadjuvant therapy. | up to 8 months | 
| Time to operation | Used for assessment of the feasibility of the neoadjuvant therapy. | up to 8 months | 
| Progression free survival | Used for assessment of the efficacy. | up to 3 years | 
| Overall survival | Used for assessment of the efficacy. | up to 3 years | 
| Incidence of adverse events | Graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. Safety will be recorded through the incidence of adverse events, serious adverse events and specific laboratory abnormalities (worst grade) in each treatment arm. | up to 3 years |