Immunotherapy and Radioembolisation for Metastatic Hepatocellular Carcinoma

Inclusion Criteria: Metastatic hepatocellular carcinoma (HCC) confirmed by radiological findings with contrast-enhanced triphasic CT scan of the liver and/or MRI scan of the abdomen, without or without histological/cytological confirmation or elevation of serum alpha-feto protein. Must be of age 18 years or above. Must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at study entry. Must be eligible to receive immune checkpoint inhibitor and yttrium-90 microsphere injection. Must have baseline efficacy images with CT or MRI and measurable target lesions in the liver according to RECIST 1.1 and mRECIST, taken within 28 days prior to the start of immune checkpoint inhibitor. Must be able to provide written informed consent. Adequate serum hematological functions defined as: Absolute neutrophil count (ANC) ≥1.0 x 10^9/l Platelet ≥75 x 10^9/l Haemoglobin ≥9 g/dL Adequate serum biochemistry functions defined as: Serum bilirubin ≤1.5 x institutional upper limit of normal (ULN). <<This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.>> Serum aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤2.5 times of institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5 times of ULN Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) Exclusion Criteria: Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment or 5 half-lives, whichever is shorter. Has a diagnosis of severe active scleroderma, lupus, other rheumatologic or autoimmune disease within the past 3 months before study recruitment. Patients with a documented history of clinically severe autoimmune disease or a syndrome requiring systemic steroids or immunosuppressive agents will not be allowed on this study. Subjects with vitiligo or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections are not excluded from the study. Subjects with hypothyroidism stable on hormone replacement are not excluded from this study. Has had a prior monoclonal antibody, immunotherapy or immune checkpoint inhibitors before recruitment into this study. Has had prior chemotherapy or targeted small molecule therapy (including sorafenib or other anti-vascular endothelial growth factor inhibitor) within 3 weeks prior to administration of the study drug or who has not recovered (i.e., grade ≤1 or at baseline) from adverse events due to a previously administered agent. Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, indolent lymphomas, or in situ cervical cancer that has undergone potentially curative therapy. Has known carcinomatous meningitis (also known as leptomeningeal carcinomatosis). Has an active infection requiring intravenous systemic therapy or hospital admission. Has a history or current evidence of any condition, therapy, or laboratory abnormality, including psychiatric or substance abuse disorder, that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 31 weeks after the last dose of trial treatment. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies). Routine checking for Anti-HIV1 or Anti-HIV2 is not mandatory. Untreated hepatitis B infection. Patients with chronic hepatitis B infection (defined as HBsAg positive) are eligible if they have started anti-viral therapy for at least 1 month and is continuing anti-viral treatment throughout the whole duration of this study. Has experienced Grade 4 toxicity on treatment with prior radiation. Has experienced grade 3-4 intracranial toxicity (hypophysitis or central nervous system toxicity) with either prior intracranial radiation, anti-programmed cell death-1 (PD-1), or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor therapy. Is taking >4mg/day of dexamethasone or its equivalent at the start of immunotherapy or has required >4mg/day of dexamethasone or its equivalent for 3 consecutive days within 1 week of starting treatment. Allergies and adverse drug reaction to the following: History of allergy to study drug components; History of severe hypersensitivity reaction to any monoclonal antibody. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study medication. Note: Local surgery of isolated lesions for palliative intent is acceptable. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥470 ms calculated from 3 ECGs (within 15 minutes at 5 minutes apart). Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion: (A) Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) (B) Systemic corticosteroids at physiologic doses not to exceed <<10 mg/day>> of prednisone or its equivalent (C) Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication)