TheraSphere With Durvalumab and Tremelimumab for HCC

The objective of the ROWAN clinical study is to assess the efficacy of local tumor control in HCC patients who receive TheraSphere followed by durvalumab and tremelimumab.

Inclusion Criteria: 1. Participants must be aged ≥18 years at the time of screening. 2. Written informed consent and any locally required authorization (e.g., Health Insurance Portability and accountability Act in the US, European Union (EU) data privacy regulations in the EU) obtained from the patient/legal representative prior to performing any protocol-related procedures, including screening evaluations. 3. Life expectancy ≥6 months. 4. HCC, diagnosed by radiographic imaging or histology. 5. Patient not a candidate for liver resection, thermal ablation, or transplantation at the time of study entry. 6. ECOG 0 or 1 7. Measurable disease by mRECIST criteria (e.g. ≥10mm of enhancement). 8. Tumor volume ≤35% of whole liver volume (determined by imaging). 9. Future liver remnant volume (FLRV) ≥30% of whole liver volume. FRLV is the volume of liver not planned to be treated with TheraSphere and free of HCC. 10. Dosimetry criteria for tumor(s) and normal tissue can be determined. 11. Patients with previous liver resection or ablation ≥6 months from end of previous treatment to TheraSphere administration. 12. Previous transarterial chemoembolization (TACE) is permitted if: 1. Previous TACE performed ≥8 months before TheraSphere administration and 2. Result of previous TACE was CR and 3. Current tumor is not a recurrence of previously treated lesion 13. Patients with portal vein thrombosis (PVT) Vp0, Vp1, or Vp2. 14. Patients with HBV or HCV infection are to have documented virology status of hepatitis as confirmed by HBV and HCV serology test: 1. Patients with HBV infection: HBV DNA load should be ≤2000 IU/mL obtained within 42 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study 2. Patients with chronic HCV infection are allowed in the study: for untreated patients, AST/ALT should be ≤3xULN and for treated patients, antiviral treatment (per local standard of care) should be stopped for a minimum of 14 days prior to study entry and AST/ALT should be ≤3xULN 15. Patients with Human Immunodeficiency Virus (HIV) infection are eligible, provided the HIV infection is well controlled with no current or previous AIDS-related complications and CD4+ T-cell (CD4+) counts ≥ 350 cells/uL 16. Negative serum pregnancy test in females of childbearing potential. 17. Adequate contraception for the patient and his/her sexual partner. 18. Adequate renal and marrow function as defined below: 1. Hemoglobin (hgB) ≥9.0 g/dL 2. Absolute neutrophil count (ANC) ≥1.5 x 109/L 3. Platelet count ≥75 x 109/L 4. Measured or calculated creatinine clearance ≥45 mL/min as determined by Cockcroft-Gault (using actual body weight) 19. Absolute lymphocyte count ≥0.5 X 109/L 20. Adequate liver function, as defined by 1. Child-Pugh A 2. Albumin-bilirubin (ALBI) score 1 or 2 with upper limit for ALBI score ≤ -2. Patients with confirmed Gilbert's syndrome may not have an evaluable bilirubin value; therefore, ALBI score should not be considered for such patients. Patients with Gilbert's syndrome will be eligible with any bilirubin value, as long as Albumin level is ≥ 34 g/L. 3. AST and ALT \30 kg and BMI ≥18 kg/m2. Exclusion Criteria: 1. Any contraindication to angiography or selective visceral catheterization. 2. Cone Beam CT (CBCT) or Technetium-99m macroaggregated Albumin (99mTc-MAA) hepatic arterial perfusion scintigraphy shows any deposition to the gastrointestinal tract that may not be corrected by angiographic techniques. 3. 99mTc-MAA hepatic arterial perfusion scintigraphy shows poor tumor and/or portal vein thrombosis (PVT) targeting that would lead to a dose that does not meet the liver dosing criteria. 4. Shunting of blood to the lungs that could result in delivery of \>30 Gy to the lungs in a single treatment or \>50 Gy cumulative dose to the lungs in case of multiple TheraSphere treatments, as seen on 99mTc-MAA hepatic arterial perfusion scintigraphy. 5. Vp3, Vp4, hepatic vein invasion, or inferior vena cava (IVC) invasion 6. Extrahepatic metastases (patients with extrahepatic spread \[EHS\]): 1. EHS is any extrahepatic lesion that, according to clinical symptoms, histology, or imaging data, is highly suspicious of being metastases. 2. For patients with bone pain/neurological symptoms (deficit, seizure or else) at baseline and suspected of metastases at screening, a bone scan/brain MRI is recommended prior to study entry. 3. Extrahepatic non-target non-measurable lesions (\