An Open-Label, Single Arm Study to Evaluate the Efficacy and Safety of Adebrelimab Plus Apatinib as Adjuvant Therapy in Participants With Hepatocellular Carcinoma at High Risk of Recurrence After Surgical Resection
Overview
- Phase
- Phase 2
- Intervention
- Adebrelimab + Apatinib
- Conditions
- Carcinoma, Hepatocellular
- Sponsor
- Qilu Hospital of Shandong University
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- RFS Rate at 12 and 24 Months
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
This is a single-center, single-arm, open-label clinical study to evaluate the efficacy and safety of Adebrelimab plus Apatinib as adjuvant therapy in hepatocellular carcinoma (HCC) participants who are at high risk of recurrence after curative resection.
Detailed Description
Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. Surgical resection is the most important radical treatment. However, the recurrence rate is high especially in the participants with high risk of recurrence after curative resection. Adebelimumab is a humanized anti-PD-L1 monoclonal antibody independently developed by Hengrui Pharmaceutical. It can specifically bind to PD-L1 molecules to block the PD-1/PD-L1 pathway that leads to tumor immune tolerance, reactivate the anti-tumor activity of the immune system, and achieve the goal of treating tumors. As of October 8, 2021, adebelimumab has conducted several clinical studies in various malignant tumor fields and has shown good anti-tumor efficacy and controllable safety. Therefore, the investigators plan to conduct a prospective clinical study targeting HCC participants at high risk of postoperative recurrence, to demonstrate the efficacy and safety of postoperative adjuvant therapy with adebelimumab combined with apatinib. This study has the potential to provide efficient new treatment options for participants, which is of great significance for improving the survival rate and quality of life of liver cancer participants in general. A mid-term analysis will be conducted on the recurrence free survival rate and survival rate, at 6 months after the enrollment of 30 participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants must meet all of the following conditions in order to be enrolled in this study:
- •Voluntarily participate in this study and sign an informed consent form.
- •Participants diagnosed with HCC through pathological histology/cytology or clinically diagnosed with HCC according to the Diagnosis and Treatment Guidelines for Primary Liver Cancer (2024 Edition).
- •Within 4-12 weeks prior to enrollment, radical resection surgery was performed.
- •Complete recovery from surgical resection within 4 weeks prior to enrollment.
- •High risk factors for postoperative recurrence of hepatocellular carcinoma include multiple tumors, tumor length\>5 cm, poor tumor differentiation (Edmondson III-IV grade), margin ≤ 1 cm, invasion of Microvasculature or large vessels, lymph node metastasis, sustained abnormalities in AFP or abnormal prothrombin , etc.
- •Child Pugh liver function rating within 7 days prior to randomization: A or B (≤ 7 points).
- •ECOG PS score within 7 days before randomization: 0-1 points.
- •Have not received systematic anti-tumor treatment for hepatocellular carcinoma in the past.
- •Expected survival time ≥ 12 weeks.
Exclusion Criteria
- •If a subject meets any of the following conditions, they will not be allowed to enter this study:
- •Known hepatobiliary carcinoma, sarcoma like hepatocellular carcinoma, combined hepatocellular-cholangiocarcinoma，and fibrous layer cell carcinoma; Within 5 years or simultaneously suffering from other active malignant tumors other than hepatocellular carcinoma (excluding cured skin basal cell carcinoma and cervical carcinoma in situ).
- •There are uncontrollable extrahepatic metastases, such as lung and brain metastases (EHS).
- •Previously received local treatment, including therapeutic TACE, transarterial embolization (TAE), hepatic artery infusion chemotherapy (HAIC), transarterial radiation embolization (TARE), etc.
- •Participants who are preparing to undergo or have previously received organ or allogeneic bone marrow transplantation.
- •Participants who are currently accompanied by interstitial pneumonia or interstitial lung disease, or have a history of interstitial pneumonia or interstitial lung disease that requires hormone therapy in the past, or other pulmonary fibrosis, organized pneumonia (such as bronchiolitis obliterans), pneumoconiosis, drug-related pneumonia, idiopathic pneumonia, or subjects with evidence of active pneumonia or severe lung function impairment seen on chest computed tomography (CT) images during screening, are allowed to have radiation induced pneumonia in the radiation field; Active tuberculosis.
- •Currently, there is active autoimmune disease or a history of autoimmune disease that may recur (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, pituitary inflammation, vasculitis, nephritis, hyperthyroidism, hypothyroidism \[subjects that can be controlled only through hormone replacement therapy can be included\]); Subjects with skin diseases that do not need systematic treatment, such as vitiligo, psoriasis, alopecia, controlled type I diabetes that receive insulin treatment, or childhood asthma that has completely alleviated without any intervention after adulthood can be included; Asthma subjects who require medical intervention with bronchodilators cannot be included.
- •Suffering from hypertension and unable to achieve good control through antihypertensive drug treatment (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) (based on the average BP reading obtained from ≥ 2 measurements), it is allowed to achieve the above parameters through the use of antihypertensive therapy; Previously experienced hypertensive crisis or hypertensive encephalopathy.
- •Participants with moderate to severe ascites with clinical symptoms who require therapeutic puncture or drainage, or whose Child Pugh score is greater than 7 (excluding those who only show a small amount of ascites on imaging but do not have clinical symptoms); Uncontrolled or moderate to equal amounts of pleural effusion and pericardial effusion.
- •There are clinical symptoms or diseases of the heart that cannot be well controlled, such as: (1) According to the standards of the New York Heart Association (NYHA), level II or above cardiac insufficiency or cardiac ultrasound examination: LVEF (left ventricular ejection fraction)\<50%; (2) Unstable angina pectoris; (3) Have experienced myocardial infarction within one year prior to the start of the research treatment; (4) Clinically significant supraventricular or ventricular arrhythmias require treatment or intervention; (5) QTc\>480ms (QTc interval is calculated using the Fridericia formula; if QTc is abnormal, it can be detected continuously three times every 2 minutes, and the average value is taken).
Arms & Interventions
Adebrelimab + Apatinib
Intervention: Adebrelimab + Apatinib
Outcomes
Primary Outcomes
RFS Rate at 12 and 24 Months
Time Frame: up to 24 months
Recurrence-free survival rate at 12 and 24 Months
Secondary Outcomes
- recurrence-free survival(up to 3 years)
- overall survival(3 years)
- Time to Recurrence(up to 3 years)