A Trial of Cadonilimab Plus Regorafenib in Patients With Hepatocellular Carcinoma Who Failed Camrelizumab Combined With Apatinib

A Single-arm, Multicenter, Phase II Trial of Cadonilimab Plus Regorafenib in Patients With Hepatocellular Carcinoma Who Progressed on Camrelizumab Combined With Apatinib

To evaluate the efficacy and safety of cadonilimab combined with Regorafenib in patients with hepatocellular carcinoma who failed camrelizumab plus apatinib.

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Cadonilimab+regorafenib

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Fujian
    • Fuzhou, Fujian, China
      • Recruiting
      • Mengchao Hepatobiliary Hospital, Fujian Medical University
      • Contact: Yong yi Zeng; Phone Number: 0591-88112829; Email: lamp197311@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Sign a written informed consent form before enrollment;
2. Age >18 years old, both sex;
3. Histological or pathological confirmed intermediate or advanced hepatocellular carcinoma, or patients with cirrhosis who meet the clinical diagnostic criteria for hepatocellular carcinoma of the American Association for the Study of Liver Diseases (AASLD);
4. Have progressed on the combination treatment of camrelizumab and apatinib for HCC
5. Child-Pugh Class A;
6. ECOG PS score: 0~1;
7. At least 1 measurable lesion (RECIST1.1)
8. Expected survival period≥12 weeks
9. The function of vital organs meets the following requirements (excluding the use of any blood components and cell growth factors within 14 days):

1. Blood routine: Neutrophils≥1.5×109/L Platelet count ≥75×109/L Hemoglobin ≥ 90g/L; 2. Liver and kidney function: Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 50 ml/min (Cockcroft-Gault formula); Total bilirubin (TBIL) ≤ 3 times the upper limit of normal (ULN); Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 10 times the upper limit of normal (ULN); urine protein < 2+; if urine protein ≥ 2+, 24-hour urine protein quantification shows that the protein must be ≤ 1g; 10. Normal coagulation function, no active bleeding or thrombosis disease

1. International normalized ratio INR≤1.5×ULN;
2. Partial thromboplastin time APTT≤1.5×ULN;
3. Prothrombin time PT≤1.5×ULN; 11. Non-surgical sterilization or female patients of childbearing age 12. Subjects voluntarily join this study, have good compliance, and cooperate with safety and survival follow-up

Main Exclusion Criteria:

1. Containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma that have been previously confirmed by histology/cytology;
2. Have a history of hepatic encephalopathy;
3. Have a history of liver transplantation;
4. There is clinically significant pericardial effusion, and there are clinical symptoms of pleural effusion that require drainage;
5. Clinically apparent ascites is defined as meeting the following criteria: ascites can be detected by physical examination during screening or ascites needs to be drained during screening;
6. Simultaneous infection with HBV and HCV (having a history of HCV infection but negative HCV RNA can be considered as not being infected with HCV);
7. Presence of central nervous system metastasis or meningeal metastasis
8. Bleeding from esophageal or gastric varices caused by portal hypertension has occurred within 6 months before the first dose
9. Patients with any bleeding or bleeding event ≥CTCAE grade 3 within 4 weeks before the first dose
10. Arterial and venous thromboembolic events occurred within 6 months before the first dose
11. Uncontrolled high blood pressure
12. Symptomatic congestive heart failure
13. Severe bleeding tendency or coagulation disorder
14. Have a history of gastrointestinal perforation and/or fistula, intestinal obstruction within 6 months before the first dose
15. Active autoimmune disease or a history of autoimmune disease
16. Patients with HIV
17. According to the investigator's judgment, patients with other serious concomitant diseases that endanger the patient's safety or affect the patient's completion of the study.

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: cadonilimab+regorafenib	Drug: Cadonilimab+regorafenib; cadonilimab: 6mg/kg iv D1 Q2W; regorafenib: 80mg QD oral; Eligible patients will receive cadonilimab combined with regorafenib, until disease progression or intolerable toxicity or death or withdrawal of informed consent, whichever occurred first

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate (ORR) per RECIST1.1	The proportion of all subjects with the best overall response (BOR) as complete remission (CR) or partial remission (PR) according to RECIST 1.1 criteria.	Up to two years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival（PFS）	PFS was defined as the time from the first dose to the time of the first documented tumor progression (assessed by RECIST1.1 criteria) or the time of death from any cause, whichever occurred first.	Up to two years
Overall survival（OS）	Defined as the time from the first dose to the death from any cause.	Up to three years
Duration of response (DOR)	Defined as the time from the first dose to disease progression or death in patients who achieve complete or partial response	Up to two years
Occurence of AE and SAE	Occurence of Adverse Event (AE) and Serious Adverse Event (SAE) （NCI CTCAE 5.0）	Up to two years

Collaborators and Investigators

• Sponsor: Meng Chao Hepatobiliary Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: February 19, 2024
• First Submitted That Met QC Criteria: February 19, 2024
• First Posted (Actual): February 28, 2024

Study Record Updates

• Last Update Posted (Actual): May 15, 2025
• Last Update Submitted That Met QC Criteria: May 12, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: cadonilimab (anti PD-1/CTLA-4 bispecific antibody)
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: 2023_148_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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