Hepatic Artery Infusion of Adebrelimab Combined With Bevacizumab in the Treatment of Advanced Hepatocellular Carcinoma With Failure of Systemic Therapy Combined With Interventional Therapy

Sponsor

HuiKai Li (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05975463

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The goal of this prospective single arm, Phase II Clinical Study is to explore and evaluate the efficacy and safety of hepatic artery infusion of adebelimab combined with Bevacizumab in the treatment of patients with advanced hepatocellular carcinoma who failed in systematic therapy combined with interventional therapy.

Participants willThe enrolled patients will receive hepatic artery infusion of adebelimab 1200mg, d1, q3w, combined with hepatic artery infusion of Bevacizumab 5mg/kg, d1, q3w, HAIC treatment for 3-4 times.

Condition or Disease	Intervention/Treatment	Phase
Hepatocellular Carcinoma	Procedure: HAIC Drug: Adebrelimab Drug: Bevacizumab	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Prospective Single Arm, Single Center, Phase II Clinical Study of Hepatic Artery Infusion of Adebrelimab Combined With Bevacizumab Treatment System for Advanced Hepatocellular Carcinoma With Failure of Systemic Therapy Combined With Interventional Therapy

Anticipated Study Start Date :

Jul 31, 2023

Anticipated Primary Completion Date :

Jul 31, 2025

Anticipated Study Completion Date :

Jul 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HAIC+Adebrelimab+Bevacizumab hepatic artery infusion of Adebrelimab 1200mg, d1, q3w, combined with hepatic artery infusion of Bevacizumab 5mg/kg, d1, q3w, HAIC treatment for 3-4 times.	Procedure: HAIC hepatic artery infusion for 3-4 times. Drug: Adebrelimab hepatic artery infusion of Adebrelimab 1200mg, d1, q3w，for 3-4 times. Drug: Bevacizumab hepatic artery infusion of Bevacizumab 5mg/kg, d1, q3w, for 3-4 times.

Arm

Intervention/Treatment

Experimental: HAIC+Adebrelimab+Bevacizumab

hepatic artery infusion of Adebrelimab 1200mg, d1, q3w, combined with hepatic artery infusion of Bevacizumab 5mg/kg, d1, q3w, HAIC treatment for 3-4 times.

Procedure: HAIC

hepatic artery infusion for 3-4 times.

Drug: Adebrelimab

hepatic artery infusion of Adebrelimab 1200mg, d1, q3w，for 3-4 times.

Drug: Bevacizumab

hepatic artery infusion of Bevacizumab 5mg/kg, d1, q3w, for 3-4 times.

Outcome Measures

Primary Outcome Measures

ORR [Up to one year]
Objective response rate

Secondary Outcome Measures

PFS [Up to two years]
Progression-free survival：The time from the start of treatment to the progression of the disease or death from any cause
OS [Up to two years]
Overall Survival：The survival time from enrollment to death from any cause.
DCR [Up to one year]
Disease Control Rate: (Ratio of CR+PR+SD)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

1. Non resectable advanced hepatocellular carcinoma confirmed by pathological and clinical imaging examinations.
1. Patients who have previously received systematic treatment combined with failed or intolerable interventional therapy.
1. Male or female, aged ≥ 18 years at the time of signing the ICF.
1. The liver should have at least one measurable target lesion (RECIST v1.1). If it is an active lesion after local treatment (radiotherapy, ablation, TACE, etc.), local treatment should be completed 4 weeks before the screening period imaging examination.
1. The patient's Eastern Oncology Collaborative Group (ECOG) physical condition score is 0 or 1.
1. The patient's organ and blood system functions meet the requirements:

Hematology function: Absolute neutrophil count (ANC) ≥ 1.5 x 10 ^ 9/L, platelet count ≥ 75 x 10 ^ 9/L
Adequate renal function: serum creatinine<1.5x ULN or creatinine clearance rate>40 mL/min (Cockcroft Fault formula)
Liver function: Total bilirubin ≤ 1.5 x ULN, AST and ALT ≤ 5 x ULN
Coagulation function: Within the normal range of PT time.

1. Female subjects with Fertility need to carry out serum pregnancy test within 72 hours before starting the study drug administration, and the result is negative, and take effective contraceptive measures (such as Intrauterine device, contraceptive pill or pregnancy avoidance condom) during the test period and at least 3 months after the last administration; For male subjects whose partners are Fertility women, they should be surgically sterilized or agree to take effective contraceptive measures during the trial period and within 3 months after the last administration.
1. The subjects have good compliance and cooperate with follow-up.

Exclusion Criteria:

1. Has a history of allergies to any component of the study drug in the past;
1. Known to be allergic to PD-1/PD-L1 antibodies or have experienced drug-related irAEs in the past, in accordance with the "Toxicity Management Guidelines for CSCO Immunocheckpoint Inhibitors 2019", it meets the indication for permanent discontinuation of medication;
1. There are known Contraindication of percutaneous hepatic artery infusion;
1. Has received or is currently receiving any of the following treatments in the past:

The patient underwent major surgical procedures within 14 days prior to entering the study (puncture biopsy is not included)
Previous or planned immune therapy such as CAR-T and vaccines

1. Have any active autoimmune disease or history of autoimmune disease, including but not limited to interstitial pneumonia, enteritis, hepatitis, hypophysitis, Vasculitis, nephritis, hyperthyroidism, hypothyroidism (it can be considered to be included after hormone replacement treatment); Patients with psoriasis or childhood asthma/allergy that has completely alleviated and does not need any intervention after adulthood can be considered for inclusion, but patients who need medical intervention with Bronchiectasis cannot be included;
1. Poor nutritional status, BMI<18.5 Kg/m2; If symptomatic nutritional support is provided and corrected before enrollment, and evaluated by the main investigator, enrollment can continue to be considered;
1. Have a history of immune deficiency, including positive Diagnosis of HIV/AIDS, or have other acquired or congenital immune deficiency diseases, or have a history of organ transplantation or allogeneic bone marrow transplantation;
1. There are clinical symptoms or diseases of the heart that cannot be well controlled, including but not limited to: (1) NYHA grade II or above heart failure, (2) unstable angina pectoris, (3) myocardial infarction within 1 year, (4) clinically significant supraventricular or ventricular arrhythmias that have not undergone clinical intervention or are still poorly controlled after clinical intervention;
1. Serious infection (CTCAE>grade 2) occurred within 4 weeks before the first use of the study drug, such as severe pneumonia, Bloodstream infections, infection complications, etc. requiring hospitalization; Baseline chest imaging examination indicates the presence of active pulmonary inflammation, symptoms and signs of infection within 14 days prior to the first use of the study drug, or the need for oral or intravenous antibiotic treatment, excluding prophylactic use of antibiotics;
1. Those who have been found to have active pulmonary tuberculosis infection through medical history or CT examination, or have a history of active pulmonary tuberculosis infection within 1 year before enrollment, or have a history of active pulmonary tuberculosis infection more than 1 year before but have not received formal treatment;
1. There is active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL) and hepatitis C (hepatitis C antibody is positive, and HCV RNA is higher than the detection limit of the analytical method);
1. Other malignant tumors were diagnosed within 5 years before the first use of the study drug, except for malignant tumors with low risk of metastasis or death (5-year survival rate>90%), such as fully treated skin Basal-cell carcinoma or squamous cell skin cancer or cervical Carcinoma in situ, which can be considered to be included in the group;
1. Pregnant or lactating women;
1. Previous history of hypertensive crisis or hypertensive encephalopathy;
1. Use Nonsteroidal anti-inflammatory drug (NSAIDs) for long-term daily treatment;
1. Untreated or incompletely treated esophageal and/or gastric varices with high risk of bleeding or bleeding;
1. Previous bleeding events caused by esophageal and/or gastric varices within 6 months prior to the start of the study treatment;
1. According to the judgment of the researchers, there are other factors that may lead to forced termination of the study, such as suffering from other serious illnesses (including mental illness) requiring concurrent treatment, alcoholism, drug abuse, family or social factors, which may affect the safety or compliance of the subjects.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tianjin Cancer Hospital Airport Hospital	Tianjin	Tianjin	China	300308

Sponsors and Collaborators

HuiKai Li

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

HuiKai Li, Director, Tianjin Medical University Cancer Institute and Hospital

ClinicalTrials.gov Identifier:

NCT05975463

Other Study ID Numbers:

SHR1316-HCC-TJ-001

First Posted:

Aug 4, 2023

Last Update Posted:

Aug 4, 2023

Last Verified:

Jul 1, 2023

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Carcinoma

Carcinoma, Hepatocellular

Bevacizumab

Study Results

No Results Posted as of Aug 4, 2023