The Efficacy and Safety of Donafenib Plus PD-1/L1 Monoclonal Antibodies Plus TACE) or HAIC as First-line Treatment for Unresectable Hepatocellular Carcinoma A Multi-center, Retrospective Clinical Study

The Efficacy and Safety of Donafenib Plus PD-1/L1 Monoclonal Antibodies Plus Transarterial Chemoembolization (TACE) or Hepatic Arterial Infusion Chemotherapy (HAIC) as First-line Treatment for Unresectable Hepatocellular carcinomaA Multicenter, Retrospective Clinical Study

This is a multicenter, retrospective study planned to enroll patients with unresectable hepatocellular carcinoma (uHCC) who received first-line donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC at 8 sites between June 1, 2021 and November 30, 2024. The study consists of two cohorts: Cohort A consists of patients who received donafenib + PD-1/L1 inhibitor + TACE, and Cohort B consists of patients who received donafenib + PD-1/L1 inhibitor + HAIC, with a planned enrollment of 200 patients per cohort. Relevant data will be collected to evaluate the efficacy and safety of donafenib combined with an anti-PD-1/L1 monoclonal antibody and either TACE or HAIC in the treatment of uHCC in real-world clinical practice.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Donafeinib; Procedure: Transcatheter arterial chemoembolization; Drug: PD-1 / PD-L1 monoclonal antibody; Procedure: Hepatic Artery Infusion Chemotherapy

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

• Study Contact: Name: Zheng Wang; Phone Number: +86 021 6404 1990; Email: wang.zheng@zs-hospital.sh.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yat-sen University Cancer Center
    • Guangzhou, Guangdong, China
      • Zhujiang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China
      • Sun Yat-sen Memorial Hospital
  • Guangxi
    • Nanning, Guangxi, China
      • The First Affiliated Hospital of Guangxi Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • Harbin Medical University Cancer Hospital
      • Contact: Yingchen Li; Phone Number: +86 0451 8629 8666; Email: xiakanfanxing@163.com
  • Shandong
    • Qingdao, Shandong, China
      • The Affiliated Hospital of Qingdao University
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Zhong Shan Hospital Fudan University
  • Yunan
    • Kunming, Yunan, China
      • Yunnan Cancer Hospital

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

Patients with unresectable hepatocellular carcinoma (uHCC) who received donafenib, PD-1/L1 monoclonal antibody combined with transarterial intervention therapy (TACE or HAIC) as first line treatment.

Description

Inclusion Criteria:

• Patients with unresectable hepatocellular carcinoma (uHCC) who received donafenib, an anti-PD-1/L1 monoclonal antibody combined with transarterial interventional therapy (TACE or HAIC), with retrievable records in the hospital electronic information system between June 1, 2021 and November 30, 2024.
• Diagnosis of hepatocellular carcinoma confirmed by the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2024 Edition) clinically or by histology/cytology.
• Age ≥18 years, regardless of sex.
• No prior systemic therapy before the administration of donafenib, anti-PD-1/L1 monoclonal antibody combined with transarterial interventional therapy (TACE or HAIC).
• The maximum interval between the initiation of donafenib, anti-PD-1/L1 monoclonal antibody, and transarterial interventional therapy (TACE or HAIC) does not exceed 8 weeks, and at the time the last of these treatment modalities is initiated, the subject must not have experienced disease progression.
• For patients who have previously undergone hepatectomy, the resection must be R0, and tumor recurrence must have occurred more than 24 months after surgery.
• At least one evaluable lesion (according to RECIST v1.1 criteria).
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0 to 1.
• Child-Pugh class A or B.
• Adequate major organ function, defined by the following criteria:

Complete blood count (without blood transfusion or use of granulocyte colony-stimulating factor [G-CSF] within 14 days prior to screening):

1. Hemoglobin ≥90 g/L;
2. Absolute neutrophil count (ANC) ≥1.5×10⁹/L;

3. Platelet count ≥75×10⁹/L;

   - Blood biochemistry (without albumin use within 14 days prior to screening):

4. Albumin ≥28 g/L;
5. Total bilirubin ≤2× upper limit of normal (ULN);
6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5× ULN;
7. Alkaline phosphatase (ALP) ≤5× ULN;

8. Creatinine ≤1.5× ULN;

   - Coagulation function:

9. International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN;
10. Activated partial thromboplastin time (APTT) ≤1.5× ULN.

Exclusion Criteria:

• Incomplete or unavailable patient information data; patient refused follow-up or was lost to follow-up;
• Duration of donafenib, PD-1/L1 monoclonal antibody combined with transarterial intervention therapy was less than 1 month;
• Prior histologically/cytologically confirmed diagnosis of fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, or other components;
• History of malignancy other than hepatocellular carcinoma, unless meeting the following criteria: a) The patient received potentially curative treatment and there has been no evidence of disease for 5 years; b) Successfully treated resected cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, or other carcinoma in situ;

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; Donafenib +PD-1/L1+TACE	Drug: Donafeinib; Donafenib: 200mg Bid, or follow medical order; Procedure: Transcatheter arterial chemoembolization; Follow medical order; Drug: PD-1 / PD-L1 monoclonal antibody; Follow Drug instructions or medical order
GROUP B; Donafenib +PD-1/L1+HAIC	Drug: Donafeinib; Donafenib: 200mg Bid, or follow medical order; Drug: PD-1 / PD-L1 monoclonal antibody; Follow Drug instructions or medical order; Procedure: Hepatic Artery Infusion Chemotherapy; Follow medical orders

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
progression free survival(PFS)	Progressive disease is measured according to modified Response Evaluation Criteria in Solid Tumors	Up to approximately 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate（ORR）	CR+PR，measured according to modified Response Evaluation Criteria in Solid Tumors	up to approximately 2 years
Disease control rate（DCR）	CR+PR+SD, measured according to modified Response Evaluation Criteria in Solid Tumors	up to approximately 2 years
Overall Survival (OS）		up to approximately 2 years
Duration of Response（DOR）		up to approximately 2 years
Safety（incidence of AEs ）	Adverse events (AEs), adverse reactions and safety laboratory parameters occurring during the treatment period will be summarized according to CTCAE V5.0 grading. The incidence of AEs will be calculated, and the frequency and number of AEs will be listed by system organ class (SOC) with percentages calculated.	up to approximately 2 years

Collaborators and Investigators

• Sponsor: Shanghai Zhongshan Hospital
• Collaborators: Yunnan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028

Study Registration Dates

• First Submitted: July 21, 2026
• First Submitted That Met QC Criteria: July 21, 2026
• First Posted (Actual): July 24, 2026

Study Record Updates

• Last Update Posted (Actual): July 24, 2026
• Last Update Submitted That Met QC Criteria: July 21, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• 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: B2026-120

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