Candonilimab Plus Bevacizumab for Patients With Advanced HCC Who Progressed on A+T

Study Overview
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Brief Summary
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To explore the efficacy and safety of candonilimab plus bevacizumab for patients with advanced hepatocellular carcinoma who progressed on atezolizumab plus bevacizumab.

Detailed Description
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Atezolizumab plus bevacizumab is the first-line treatent for patients with advanced hepatocellular carcinoma. However, the second-line treatment is absent for patients who progressed on atezolizumab plus bevacizumab. Candonilimab is a humanized bisspecific monoclonal antibody against PD-1/ CTLA-4 IgG1. Candonilimab plus lenvatinib showed strong anti-tumor effect, with objective response of 44%. This single-arm, prospective, phase 2 trial is to explore the efficacy and safety of candonilimab plus bevacizumab for patients with advanced hepatocellular carcinoma who progressed on atezolizumab plus bevacizumab.

Official Title
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Candonilimab Plus Bevacizumab as Second-line Treatment for Patients With Advanced Hepatocellular Carcinoma Who Progressed on Atezolizumab Plus Bevacizumab: a Single Arm, Phase 2 Trial

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Candonilimab
* Drug: Bevacizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The diagnosis of HCC was based on the diagnostic criteria for HCC used by the European Association for the Study of the Liver (EASL) Patients must have at least one tumor lesion that can be accurately measured according to EASL criteria. Barcelona clinic liver cancer-stage C Eastern Cooperative Oncology Group performance status of 0 to 2 Patients have received atezolizumab plus bevacizumab and the tumor have progressed. Patients have not received other treatmets except for the atezolizumab plus bevacizumab. No Cirrhosis or cirrhotic status of Child-Pugh class A only Not amendable to surgical resection ,local ablative therapy and any other cured treatment. The following laboratory parameters: Hemoglobin ≥ 8.5 g/dL Total bilirubin ≤ 30mmol/L Serum albumin ≥ 32 g/L ASL and AST ≤ 5 x upper limit of normal Serum creatinine ≤ 1.5 x upper limit of normal INR ≤ 1.5 or PT/APTT within normal limits Absolute neutrophil count (ANC) >1,500/mm3 • Ability to understand the protocol and to agree to and sign a written informed consent document Exclusion Criteria: Evidence of hepatic decompensation including ascites, gastrointestinal bleeding or hepatic encephalopathy Known history of HIV History of organ allograft Known or suspected allergy to the investigational agents or any agent given in association with this trial. Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy Evidence of bleeding diathesis. Patients with clinically significant gastrointestinal bleeding within 30 days prior to study entry. Known central nervous system tumors including metastatic brain disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Candonilimab Plus Bevacizumab<br>Candonilimab 10mg/kg, Bevacizumab 15mg/kg, every 3 week | Drug: Candonilimab<br>* 10mg/kg, iv.drip, every 3 week<br>Drug: Bevacizumab<br>* 15mg/kg, iv.drip, every 3 week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DCR per RECIST 1.1 | DCR （Disease Control Rate） include complete response, partial response and stable Disease per RECIST 1.1 | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival (OS) | OS is the length of time from the date of randomization until death from any cause. | 12 months | 
| Progression free survival (PFS) | PFS is defined as the time from the date of randomization to the date of the first objectively documented tumor progression or death due to any cause. | 12 months | 
| ORR per RECIST 1.1 | Objective response rate (complete response+partial response) per RECIST 1.1 | 12 months | 
| Adverse events | Safety will be evaluated according to the NCI CTCAE Version 4.03. All observations pertinent to the safety of the study medication will be recorded on the CRF and included in the final report. | 30 days | 
| Biomarkers such as PD-L1 expression | The blood specimen and needle biopsy specimen would be collected | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular Carcinoma, Candonilimab Plus Bevacizumab, Atezolizumab Plus Bevacizumab