Overcoming Immunotherapy Resistance in Hepatocellular Carcinoma

Ki vehet részt

• Adult individuals at least 18 years old
• Unresectable multifocal or metastatic HCC, as determined by the multidisciplinary tumor board
• Subject has histologically or cytologically confirmed unresectable multifocal or metastatic HCC (all other histological types are excluded)
• Child-Pugh (CP) class A (well-compensated disease) or B ≤ 7 (acceptable functional compromise)
• Progressive HCC after failure of first-line atezolizumab-based systemic therapy
• Life expectancy ≥12 weeks per investigator assessment
• At least one non-targeted measurable lesion per RECIST version 1.1 (the irradiated/targeted lesion in both cohorts will not be considered as measurable)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Agree to undergo multiple tumor biopsies, CT imaging, and blood withdrawals
• Adequate baseline laboratory results (defined as a hemoglobin ≥5.0 mmol/l, an absolute neutrophil count ≥1.5 x 109/l, platelet count ≥75 x 109/l, creatinine clearance ≥30 ml/min, bil-irubin <3x ULN and liver transaminases ALT and AST <5x ULN)
• Allowance of temporary cessation of anticoagulants (no bridge therapy)
• Subjects must voluntarily sign and date the informed consent forms
• Informed consent must be signed prior to any single study-related activity

Ki nem vehet részt

• Subjects who have received palliative radiation therapy after disease progression upon first-line treatment with atezolizumab and bevacizumab (note: prior palliative radiation therapy before or during treatment with atezolizumab and bevacizumab is allowed, provid-ed the final dose was administered ≥6 weeks before enrollment)
• Subjects who have received holmium-166 or yttrium-90 TARE after disease progression up-on first-line treatment with atezolizumab and bevacizumab (note: prior TARE before treat-ment with atezolizumab and bevacizumab is allowed)
• Previous surgical hepatico-enterostomy
• Requirement for immunosuppressive doses of systemic corticosteroids (>10 mg/day prednisone equivalents) or other systemic immunosuppressive medication
• History of other malignancies within 3 years prior to screening, except for malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%)
• Evidence of bleeding diathesis or clinically significant coagulopathy
• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Large arterio-portal venous shunting per investigator assessment
• Lung shunt fraction >10%
• The presence of significant ascites
• Pregnancy or inadequate anticonception