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

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)

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)

Study Overview

• Status: Terminated
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Toripalimab (JS001 ); Drug: Toripalimab (JS001 ) Lenvatinib

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Jia Fan; Phone Number: +86-021-64041990; Email: fan.jia@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Zhongshan Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; 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 ); Given IV
Experimental: Group B (Toripalimab, Lenvatinib); 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; Given IV 4 mg capsules
Active Comparator: Group C (Toripalimab, Lenvatinib); 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; Given IV 4 mg capsules

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

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2019
• Primary Completion (Actual): August 8, 2023
• Study Completion (Actual): August 8, 2023

Study Registration Dates

• First Submitted: March 1, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 8, 2019

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 24, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Lenvatinib
• Other Study ID Numbers: JS001-020-Ib-HCC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No