Toripalimab Combined With Donafenib in the Treatment of Advanced Hepatocellular Carcinoma

Study Overview
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Brief Summary
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This study is an open, multi-center phase I/II clinical study.

Detailed Description
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It will explore the tolerability (phase I) and effectiveness (phase II) of the Donafenib tosilate tablets combined with Toripalimab injection in patients with advanced HCC. The study is conducted in two phases, the first phase is the dose exploration phase (phase I), and the second phase is the dose expansion phase (phase II).

Official Title
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A Multi-center, Open, Dose Exploration and Dose Expansion Phase I/II Clinical Study of Toripalimab（JS001） Combined With Donafenib in Patients With Advanced Hepatocellular Carcinoma

Conditions
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Advanced Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Donafenib Tosilate Tablets
* Drug: Toripalimab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with locally advanced or metastatic HCC who are not suitable for surgical resection, who are clinically diagnosed or confirmed by histopathology and/or cytology according to the Standards for the Diagnosis and Treatment of Primary Liver Cancer (2017); At least one measurable lesion (according to RECIST v1.1); ECOG performance status score of 0 or 1; Life expectancy ≥ 12 weeks； Have not received systemic therapy (systemic chemotherapy and/or molecular targeted therapy).If the patient has received adjuvant chemotherapy after local treatment, the chemotherapy needs to be over for more than 12 months, and disease progression or metastasis occurs； Fully understand this research and voluntarily sign the ICF。 Exclusion Criteria: Patients with diffuse liver cancer, hepatic encephalopathy that is difficult to control, and liver cancer patients whose lesion size accounts for 70% or more of the entire liver. Patients with intrahepatic cholangiocarcinoma (ICC) or HCC-ICC mixed type； Tumor invades inferior vena cava VP4.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS001+Donafenib<br>Donafenib 100mg QD/100 mg BID/200 mg BID orally + JS001 240mg Q3W iv | Drug: Donafenib Tosilate Tablets<br>* In the dose exploration phase (phase I)，three doses of Donafenib tosylate tablets [100 mg once a day (QD); 100 mg twice a day (BID); 200 mg, BID] will be explored. In the dose expansion phase (phase II), patients will be treated at the recommended dose for phase 2(RP2D).The RP2D will be determined by the dose escalation study.<br>* Other names: Donafenib;Drug: Toripalimab Injection<br>* JS001 will be administrated by intravenous (i.v.) infusion once every 21 days<br>* Other names: JS001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose limiting toxicity (DLT) | Severe toxicity that may be related to JS001 or donafenib during dose escalation of phase I clinical trial | 28 days after the first dose of JS001 and Donafenib | 
| Objective response rate（ORR） as determined by the Invertigator using RECIST V1.1 | The ratio of patients who are evaluated as CR or PR | From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-JS001 antibody |  | From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months | 
| Overall survival (OS) | The Kaplan-Meier survival from the initiation date of first cycle until death from any cause or the last follow-up date. | From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months | 
| Progression free survival (PFS) | The Kaplan-Meier survival from the initiation date of first cycle until the date of first documented progression or date of death | From the time of initial administration until intolerant toxicity, disease progression, withdrawal of ICF, loss of follow-up, death or early study termination occurs (whichever occurs first),assessed up to 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCC