Study of Donafenib Combined With Tislelizumab in the Adjuvant Treatment of Primary HCC With High Risk of Recurrence

Study Overview
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Brief Summary
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To explore the safety and preliminary efficacy of donafenib combined with tislelizumab in adjuvant therapy after radical surgical resection of primary hepatocellular carcinoma with high risk of recurrence.

Detailed Description
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This study is a single-center, single-arm, open-label clinical study. For HCC patients who the investigator believes can benefit from adjuvant treatment with donafenib combined with PD-1 monoclonal antibody, they will sign an informed consent form, and then start donafenib within 1-2 months after radical surgery (stable disease assessment or improvement). Adjuvant therapy with fenib combined with tislelizumab for 6 months, to explore the safety and efficacy of postoperative adjuvant therapy with donafenib combined with tislelizumab.

Official Title
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Clinical Study of Donafenib Combined With Tislelizumab in the Adjuvant Therapy of High-risk Recurrence-risk Primary Hepatocellular Carcinoma After Radical Surgical Resection

Conditions
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Hepatocellular Carcinoma

Intervention / Treatment
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* Drug: Donafenib + Tislelizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18   75 years old (including the threshold value), male or female; Received radical resection of liver cancer 4-8 weeks before enrollment; Pathologically diagnosed as hepatocellular carcinoma and assessed by the investigator to have a high risk of recurrence; No recurrence or metastasis was confirmed by imaging examination before enrollment; Child-Pugh score of liver function A; Eastern Cooperative Oncology Group (ECOG) physical status (PS) score of 0-1; The expected survival period is not less than 3 months; The doctor's decision to use Donafenib must be done before the patient is enrolled in the study; For HBV-infected patients, if HBV-DNA is ≥104copies/ml within 14 days before enrollment, they should take antiviral treatment (entecavir is recommended), and then enter the study when it drops to <104copies/ml, and continue antiviral treatment and monitoring Liver function and serum HBV-DNA level; Have sufficient organ functional reserve Female patients with reproductive potential (referring to nonmenopausal or surgical sterilization), the serum pregnancy test results must be negative within 7 days before the administration of the study drug; female or male patients with reproductive potential, during the use of the study drug And within 60 days after the last dose, reliable contraceptive measures must be used; Patients are voluntarily enrolled, can provide written informed consent, and can understand and comply with the experimental protocol, taking medication and follow-up. Exclusion Criteria: Pathologically diagnosed as mixed hepatocellular carcinoma-intrahepatic cholangiocarcinoma (HCC-ICC) or fibrolamellar hepatocellular carcinoma; Past or current patients with congenital or acquired immunodeficiency diseases; Active or previously recorded autoimmune diseases or inflammatory diseases, with vitiligo or asthma that has been completely resolved in childhood, without any intervention in adulthood can be included; Combined with other liver diseases, including uncontrolled alcoholic hepatitis or other hepatitis, decompensated liver cirrhosis, severe fatty liver, hereditary liver disease, liver atrophy, superior vena cava syndrome, portal hypertension. Have a history of idiopathic pulmonary fibrosis, organizing pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia, idiopathic pneumonia, or evidence of active pneumonia found during chest CT scan screening; Other malignancies within 5 years, unless the patient has received potentially curative treatment and there is no evidence of the disease within 5 years, but this time requirement (that is, within 5 years) does not apply to basal cell carcinoma of the skin that has been successfully resected , skin squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ or other in situ carcinoma patients; Have a history of serious mental illness in the past; Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (such as severe vomiting, chronic diarrhea, intestinal obstruction, malabsorption, etc.); Received major surgery within 4 weeks before enrollment (determined by the investigator); Patients who have received allogeneic stem cell or solid organ transplantation in the past, including patients after liver transplantation; Received other anti-tumor systemic therapy before enrollment, including other traditional Chinese medicines with anti-tumor indications, less than 2 weeks or 5 drug half-lives (whichever is longer) after the completion of the treatment and before the drug in this study. , or patients whose adverse events caused by preoperative treatment did not recover to ≤CTCAE grade 1; Received other adjuvant therapy after surgery (except antiviral therapy); Systemic immunosuppressive drug therapy has been used within 2 weeks before enrollment, or systemic immunosuppressive drug therapy is expected to be required during the study period Concomitant use of drugs that may prolong QTc and/or induce torsades de pointes (Tdp) or drugs that affect drug metabolism; The patient is known or suspected to have a history of allergy to tyrosine kinase inhibitor (TKI) drugs and PD-1 drugs, or to the excipients of the study drug; There is uncontrollable hepatic encephalopathy, hepatorenal syndrome, ascites, pleural effusion or pericardial effusion; Active bleeding or abnormal coagulation function, bleeding tendency or receiving thrombolysis, anticoagulation or antiplatelet therapy; There is a history of gastrointestinal bleeding within the past 4 weeks or a clear tendency of gastrointestinal bleeding (such as: known local active ulcer lesions, fecal occult blood ++++ or above, such as persistent fecal occult blood+, gastroscopic examination should be performed), Or other conditions that may cause gastrointestinal bleeding as determined by the investigator (such as severe gastric fundus/esophageal varices); Gastrointestinal perforation, abdominal fistula or abdominal abscess occurred within the past 6 months; Thrombosis or thromboembolic events have occurred in the past 6 months, such as stroke and/or transient ischemic attack, deep vein thrombosis, pulmonary embolism, etc.; Cardiovascular disease with significant clinical significance, including but not limited to acute myocardial infarction, severe/unstable angina pectoris or coronary artery bypass grafting within the past 6 months, congestive heart failure (NYHA classification > grade 2 of the New York Heart Association ), poorly controlled arrhythmias that require pacemaker therapy, and uncontrolled hypertension (systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg); Active infection; Other significant clinical and laboratory abnormalities that the investigators consider to affect the safety evaluation, such as: uncontrolled diabetes mellitus, chronic kidney disease, peripheral neuropathy of grade II or above (CTCAE V5.0), abnormal thyroid function, etc.; Have not recovered from surgery, such as unhealed incisions or serious postoperative complications; Pregnant or breastfeeding women, as well as female or male patients with reproductive potential who are unwilling or unable to take effective contraceptive measures; History of alcohol, psychotropic or other drug abuse within the past 6 months; Received clinical trials of other drugs or medical devices within 4 weeks before enrollment; Unable to follow the research protocol to receive treatment or follow up regularly; Any other researchers who think that they cannot be included in the group

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Donafenib+Tislelizumab<br>Donafenib+Tislelizumab | Drug: Donafenib + Tislelizumab<br>* Donafenib 100mg, BID+Tislelizumab 200mg, D1; q3w<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1-year recurrence-free survival | Ratio of patients from first treatment to disease recurrence within 1 year | 1 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| recurrence-free survival with surgical resection | Time elapsed from surgical resection to tumor recurrence or death from any cause (if the subject died before disease recurrence) | 2 years | 
| overall survival | Time from enrollment date to date of death from any cause | up to 1 years | 
| adverse events | Incidence of adverse events in combination immunization with donafenib | up to 1 years |