Sintilimab Plus Bevacizumab Biosimilar as Neoadjuvant Therapy for Resectable Hepatocellular Carcinoma

NCT07324824 | Recruiting Phase 2 DMC

• 1 other identifier: B2024-720-01
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Surgical resection is the preferred therapeutic modality for patients with resectable hepatocellular carcinoma (HCC). However, the recurrence rate of HCC remains up to 70%. Neoadjuvant therapy for HCC could potentially reduce the risk of postoperative recurrence and prolong overall survival. Nevertheless, there is no standard neoadjuvant treatment regimen for HCC to date. In recent years, targeted therapy and immunotherapy are proved to improve the prognosis of advanced HCC patients. Previous study (ORIENT-32) has confirmed that, compared with sorafenib, sintilimab combined with bevacizumab biosimilar can delay tumor progression, reduce the risk of death, and exhibit a favorable safety profile in patients with advanced HCC. Therefore, we conducted a prospective, single-arm phase II study to investigate the efficacy of sintilimab combined with a bevacizumab biosimilar as neoadjuvant therapy in patients with resectable HCC beyond the Milan criteria.

Conditions

Hepatocellular Carcinoma; Neoadjuvant Therapy; Sintilimab; Bevacizimab

Outcome Measures

Primary Outcomes (2)

• 1-year recurrence free survival rate

  Defined as the proportion of patients who remain free from any tumor recurrence or death within 1 year after liver resection.

  Up to 2 years

• Adverse Events (AEs)

  Defined as the proportion of patients with AEs assessed by NCI CTCAE v5.0;

  Up to 2 years

Secondary Outcomes (6)

• R0 resection rate

  Up to 2 years

• pathological complete response

  Up to 2 years

• major pathological response

  Up to 2 years

• Overall survival

  Up to 2 years

• Recurrence free survival

  Up to 2 years

Study Arms (1)

sintilimab combined with bevacizumab biosimilar

EXPERIMENTAL

Drug: sintilimab combined with bevacizumab biosimilar

Interventions

sintilimab combined with bevacizumab biosimilar DRUG

Drug: Sintilimab: 200mg IV Q3W D1 (3 cycles) Drug: Bevacizumab Biosimilar: 15mg/kg, IV, Q3W, D1 (2 cycles)

sintilimab combined with bevacizumab biosimilar

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent and willing to sign an approved consent form;
• Aged ≥ 18 years;
• Clinically diagnosed or pathologically confirmed resectable hepatocellular carcinoma beyond the Milan criteria (CNLC Ib-IIa);
• No prior anti-HCC treatment;
• Child-Pugh class A.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
• Expected survival time of \> 6 months.
• Sufficient organ and bone marrow function.

You may not qualify if:

• Known as cholangiocarcinoma (ICC) or mixed hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and hepatic fibrolamellar carcinoma;
• History of organ transplantation or hepatic encephalopathy
• Pleural fluid, ascites, and pericardial effusion with clinical symptoms requiring drainage
• History of esophageal or gastric variceal bleeding caused by portal hypertension within the past 6 months; Documented severe (Grade 3) varices identified by endoscopy within 3 months prior to enrollment; Evidence of portal hypertension and assessed by the investigator as being at high risk of bleeding.
• Arterial and venous thromboembolic events in the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or any other serious thromboembolism history;
• Any life-threatening bleeding event occurring within the past 3 months;
• Severe bleeding tendency, coagulopathy, or ongoing thrombolytic therapy.
• Chronic requirement for medications that inhibit platelet function, such as aspirin (\>325 mg/day), dipyridamole, or clopidogrel.
• Uncontrolled hypertension, defined as systolic blood pressure \>140 mmHg or diastolic blood pressure \>90 mmHg despite optimal medical management; history of hypertensive crisis or hypertensive encephalopathy.
• Symptomatic congestive heart failure (New York Heart Association \[NYHA\] Functional Class II-IV); symptomatic or poorly controlled arrhythmias; history of congenital long QT syndrome; or corrected QT interval (QTc) \>500 ms at screening (calculated using Fridericia's formula).
• History of gastrointestinal perforation and/or fistula, intestinal obstruction (including incomplete obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic persistent diarrhea within the past 6 months.
• Major surgical procedure (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to enrollment; presence of unhealed wounds, ulcers, or fractures; or tissue biopsy or other minor surgical procedure within 7 days prior to enrollment, excluding venous catheterization for intravenous infusion.
• Past or current history of pulmonary diseases including pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, drug-induced pneumonia, or severe impairment of lung function.
• Active acute or chronic hepatitis B or C infection, defined as: hepatitis B virus (HBV) DNA \>2000 IU/mL or 10⁴ copies/mL; hepatitis C virus (HCV) RNA \>10³ copies/mL; or concurrent positivity for hepatitis B surface antigen (HBsAg) and anti-HCV antibodies.
• Active tuberculosis (TB); ongoing anti-TB treatment; or anti-TB treatment completed within 1 year prior to the initiation of study treatment.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: January 8, 2026
• Study Start: January 14, 2026
• Primary Completion (Estimated): January 1, 2029
• Study Completion (Estimated): January 1, 2030
• Last Updated: January 16, 2026

Record last verified: 2026-01

Locations

CN (1)