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

Sponsor

Shi Ming (Other)

Overall Status

Recruiting

CT.gov ID

NCT05760599

Collaborator

(none)

Enrollment

Location

Arm

16.1

Anticipated Duration (Months)

1.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Drug: Candonilimab Drug: Bevacizumab	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 27, 2023

Anticipated Primary Completion Date :

Jan 1, 2024

Anticipated Study Completion Date :

Jul 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Candonilimab Plus Bevacizumab Candonilimab 10mg/kg, Bevacizumab 15mg/kg, every 3 week	Drug: Candonilimab 10mg/kg, iv.drip, every 3 week Drug: Bevacizumab 15mg/kg, iv.drip, every 3 week

Arm

Intervention/Treatment

Experimental: Candonilimab Plus Bevacizumab

Candonilimab 10mg/kg, Bevacizumab 15mg/kg, every 3 week

Drug: Candonilimab

10mg/kg, iv.drip, every 3 week

Drug: Bevacizumab

15mg/kg, iv.drip, every 3 week

Outcome Measures

Primary Outcome Measures

DCR per RECIST 1.1 [12 months]
DCR （Disease Control Rate） include complete response, partial response and stable Disease per RECIST 1.1

Secondary Outcome Measures

Overall survival (OS) [12 months]
OS is the length of time from the date of randomization until death from any cause.
Progression free survival (PFS) [12 months]
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.
ORR per RECIST 1.1 [12 months]
Objective response rate (complete response+partial response) per RECIST 1.1
Adverse events [30 days]
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.
Biomarkers such as PD-L1 expression [12 months]
The blood specimen and needle biopsy specimen would be collected

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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