A Multicenter Clinical Study of Combined Therapy for Unresectable Hepatocellular Carcinoma

Exclusion Criteria20

• Diffuse HCC or presence of vascular invasion or extrahepatic spread, with the following exceptions: invasion of segmental portal vein or hepatic vein.
• Patients with Child-Pugh class C cirrhosis.
• Any contraindication to hepatic arterial embolization: Known hepatic arterial reflux; known portosystemic shunt; coagulopathy (platelet count \< 50 × 109/L, INR \> 1.5); renal failure/insufficiency requiring hemodialysis or peritoneal dialysis; known severe arteriosclerosis; complete thrombosis or complete invasion of the main portal vein.
• History of heart disease: congestive heart failure \> New York Heart Association (NYHA) class II; active coronary artery disease (CAD) (myocardial infarction ≥ 6 months prior to study initiation is permitted); arrhythmias that are difficult to control with antiarrhythmic drugs or require a pacemaker (NCI-CTCAE v5.0 \> grade 2); uncontrolled hypertension; clinically significant gastrointestinal bleeding within 4 weeks prior to initiation of study drugs.
• Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis, or pulmonary embolism, occurring within 6 months prior to the first administration of study drug, except for segmental portal vein thrombosis.
• Receipt of systemic anticancer therapy, radiotherapy, endocrine therapy, immunotherapy, or other investigational drugs within 4 weeks prior to study initiation.
• Current or prior use of immunosuppressive drugs within 28 days before the first administration of nivolumab or ipilimumab. Exceptions to this criterion include: intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular injection); physiological doses of systemic corticosteroids not exceeding 10 mg/day of prednisone or equivalent; steroids used for the prevention of allergic reactions (e.g., premedication for CT scan).
• Receipt of live attenuated vaccines within 30 days prior to the first administration of study drug (IP). Note: If the patient is enrolled, live vaccines should not be administered during the study drug treatment period and within 30 days after the last dose of the study drug.
• Major surgery within 4 weeks prior to study initiation, and the patient must have recovered from the effects of major surgery.
• Patients with a second primary malignancy, apart from adequately treated basal cell carcinoma of the skin or carcinoma in situ of the cervix, unless disease-free for more than 3 years.
• Uncontrolled comorbidities, including but not limited to persistent or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina, arrhythmia, interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhea, or psychiatric/social conditions that limit compliance with study requirements, significantly increase the risk of adverse events, or impair the patient's ability to provide written informed consent.
• Active infections, including tuberculosis (clinical assessment including medical history, physical examination, and imaging, as well as tuberculosis testing according to local practice), hepatitis B (known positive HBV surface antigen \[HBsAg\]), and hepatitis C. Patients with past or resolved HBV infection (defined as presence of hepatitis B core antibody \[anti-HBc\] and absence of HBsAg) are eligible. Patients who are HCV antibody-positive are eligible only if HCV RNA measured by PCR is negative.
• History of allogeneic organ transplantation.
• Psychiatric disorders or altered mental status that interfere with understanding the informed consent process and/or compliance with the study protocol.
• Symptomatic brain metastases. If symptoms are present, imaging is required to confirm the absence of brain metastases.
• Pregnant or breastfeeding women.
• Immunocompromised patients, such as those known to be serologically positive for human immunodeficiency virus (HIV).
• Active or previously documented autoimmune or inflammatory diseases (including inflammatory bowel disease \[such as colitis or Crohn's disease\], diverticulitis \[excluding diverticulosis\], systemic lupus erythematosus, sarcoidosis, or Wegener's granulomatosis \[granulomatosis with polyangiitis\], Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, among others).
• Known allergy or hypersensitivity to any study drug or its components.
• Currently participating in or previously participated in a study involving an investigational drug, or use of an investigational device within 4 weeks prior to the first administration of study treatment.