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

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

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

Study Overview

• Status: Withdrawn
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Candonilimab; Drug: Bevacizumab

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 Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Cancer Center Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR per RECIST 1.1	Objective response rate per RECIST 1.1	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
PD-L1 Biomarker	The blood specimen and needle biopsy specimen would be collected	12 months

Collaborators and Investigators

• Sponsor: Shi Ming

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2022
• Primary Completion (Actual): March 31, 2023
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: December 6, 2022
• First Submitted That Met QC Criteria: June 1, 2023
• First Posted (Actual): June 2, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: June 1, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Hepatocellular Carcinoma; Candonilimab Plus Bevacizumab; Atezolizumab Plus Bevacizumab
• 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; Physiological Effects of Drugs; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab
• Other Study ID Numbers: S104

Drug and device information, study documents

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