Camrelizumab Combined with Rivoceranib and Hepatic Arterial Infusion Chemotherapy (HAIC) As Conversion Therapy for Potentially Resectable Hepatocellular Carcinoma(HCC)

Camrelizumab and Rivoceranib Plus HAIC As Conversion Therapy for Potentially Resectable Intermediate-advanced Hepatocellular Carcinoma: a Multicenter, Open-label, Randomized, Phase 2/3 Study

The purpose of this phase 2/3 study is to investigate the efficacy and safety of camrelizumab combined with rivoceranib and hepatic arterial infusion chemotherapy (HAIC) as conversion therapy for Potentially Resectable HCC.

Study Overview

• Status: Not yet recruiting
• Conditions: Potentially Resectable Hepatocellular Carcinoma
• Intervention / Treatment: Drug: camrelizumab combined with rivoceranib and HAIC; Drug: camerlizumab + rivoceranib

Detailed Description

This is a multicenter, open-label, randomized study designed to evaluate the efficacy and safety of camrelizumab combined with rivoceranib and HAIC as conversion therapy.

Eligible patients will be randomized into camrelizumab + rivoceranib + HAIC group and camrelizumab + rivoceranib group. Patients in camrelizumab + rivoceranib + HAIC group will receive systemic therapy and no more than 6 cycles HAIC procedure. Tumor response assessment using CT and/or MRI will be conducted according to RECIST v1.1. Those who are assessed as CR/PR or SD and considered suitable for curative hepatic resection will receive surgry. Surgical approaches will be tailored to the individual patient according to local standards with the goal of achieving R0 resection.The first administration of postoperative camrelizumab + rivoceranib treatment is recommended to start within 4-6 weeks after surgery, requiring full recovery from the surgery prior to post-operative camrelizumab + rivoceranib treatment. Patients in camrelizumab + rivoceranib group will receive the systemic therapy until progression or unacceptable toxicity.

• Study Type: Interventional
• Enrollment (Estimated): 398
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Huichuan Sun, MD, PHD; Phone Number: sun.huichuan@zs-hospital.sh.cn; Email: sun.huichuan@zs-hospital.sh.cn

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Zhongshan Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Signed Informed Consent Form (ICF)
2. Aged ≥18 years and ≤75 years at time of signing ICF
3. Documented diagnosis of HCC confirmed by histology/cytology or clinically
4. Patients with BCLC stage B (the sum of number of tumors and the maximum diameter of the largest tumor exceeding Up-to-7 criteria) and BCLC stage C without extrahepatic metastasis: ① tumors confined to one lobe (left, right, or middle lobe), or tumors in one lobe are present alongside a single tumor with diameter ≤5 cm or up to three tumors each with diameter ≤3 cm in the remaining lobes; ②No PVTT involving the contralateral liver lobe or reaching the superior mesenteric vein. And no tumor thrombus of the inferior vena cava reaching right atrium
5. At least one measurable lesion (per RECIST v1.1) untreated lesion
6. ECOG performance status of 0 or 1
7. Child-Pugh ≤7 score
8. Life expectancy ≥12 weeks
9. Adequate organ function
10. No prior anti-tumor systemic therapies for HCC

Exclusion Criteria:

1. Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
2. Other active malignant tumor except HCC within 5 years or simultaneously
3. Prior locoregional therapy (such as TACE、TAE、HAIC、TARE)
4. There is an absolute contraindication to HAIC
5. History of hepatic encephalopathy
6. Diffuse HCC, intrahepatic tumor burden > 50%
7. PVTT reaching the superior mesenteric vein, and bilateral PVTT are present
8. Clinically significant ascites
9. Prior allogeneic stem cell or solid organ transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: camrelizumab + rivoceranib + HAIC	Drug: camrelizumab combined with rivoceranib and HAIC; systemic therapy combined with locoregional theraphy as conversion therapy
Active Comparator: camrelizumab + rivoceranib	Drug: camerlizumab + rivoceranib; systemic therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall survival (OS) after randomization, defined as the time from randomization to death from any cause	24 months
R0 rate	R0 rate defined as the proportion of patients who accomplish the complete resection of tumor with pathologically confirmed negative margin	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EFS	Event-free survival (EFS), defined as the time from randomization to progression (RECIST v1.1), recurrence and death from any cause	24 months
ORR	Objective response rate (ORR), defined as the percentage of subjects with complete response (CR) or partial response (PR) evaluated based on RECIST v1.1. CR: disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. Overall Response (OR)=CR+PR.	24 months
DCR	Disease Control Rate (DCR), defined as the percentage of subjects with complete response, partial response or stable disease (SD) ≥ 8 weeks evaluated based on RECIST v1.1. Complete response (CR) was defined as Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (PR) was defined as at least a 30% decrease in the sum of the diameter of TL, taking as reference the baseline sum of diameters. Stable disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	24 months
pCR rate	Pathological complete regression (pCR) rate, defined as the proportion of patients with no evidence of vital residual tumor cells on the complete resected specimen. pCR status will be analyzed by local pathologists at each site	24 months
MPR rate	MPR rate, defined as the proportion of patients with evidence of vital residual tumor cells <50% on the resected specimen. MPR status will be analyzed by local pathologists at each site	24 months
AE	Adverse events are graded according to the NCI-CTCAE (Version 5.0)	24 months

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Jiangsu Hengrui Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 20, 2025
• Primary Completion (Estimated): February 20, 2028
• Study Completion (Estimated): February 28, 2030

Study Registration Dates

• First Submitted: January 22, 2025
• First Submitted That Met QC Criteria: January 22, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 6, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: hepatocellular carcinoma; conversion therapy; camrelizumab and rivoceranib
• 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; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Apatinib
• Other Study ID Numbers: MA-HCC-II/III-026; 2024ZD0520401 (Other Grant/Funding Number: National Health Commission of the people's Republic of China)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No