A TheraSphere® Advanced Dosimetry Retrospective Global Study in HCC

Recently published evidence indicates a correlation between yttrium-90 dose delivered to the
tumor and normal tissue with safety and efficacy outcomes but there are no validated methods
to consistently measure dose delivered to the tumor and normal tissue. In contrast to the
standard clinical approach based on average dose to one target volume, this trial, sponsored
by Biocompatibles UK, will explore an alternative two-compartment TheraSphere dosimetry
methodology to calculate absorbed dose to tumor and normal tissue

Inclusion Criteria:

- Up to 10 well defined unilobar/bilobar HCC tumor(s) per lobe with at least one tumor
≥3 cm ± PVT

- Liver dominant disease (limited extra-hepatic metastases in the lung and/or lymph
nodes are permitted (up to 5 lesions in the lung, with each individual lesion ≤2cm;
any number of lymph node lesions with each individual lesion ≤2 cm).

- Child Pugh stage A or B7.

- BCLC A, B or C.

- Must be male or female, 18 years of age or older.

- Bilirubin ≤2 mg/dL.

- Tumor replacement <50% of total liver volume assessed by diagnostic imaging consisting
of multi-phase contrast enhanced CT or contrast enhanced MRI.

- Diagnostic imaging consisting of multi-phase contrast enhanced CT or contrast enhanced
MRI within 3 months prior to TheraSphere® administration.

- Infusion of 99mTc-MAA in a single arterial location sufficient to cover up to 10
well-defined tumors per lobe ≤ 6 weeks prior to TheraSphere® administration.

- Patients must have received TheraSphere® in a single treatment setting in one or more
arterial locations sufficient to cover up to 10 well-defined tumors based on
angiography. Subsequent TheraSphere® treatment to the second lobe may occur at least 4
weeks following the initial TheraSphere® treatment.

- For patients receiving a second TheraSphere® treatment bilirubin levels must have been
recorded prior to the second treatment

- Patients must have had clinical evaluation (assessment of liver specific AEs) and
laboratory evaluation (at least a serum bilirubin level) at baseline.

- Tumor(s), ≥3 cm, measurable by mRECIST and RECIST 1.1 at baseline

Exclusion Criteria:

- Prior external beam radiation treatment to the liver.

- Prior loco-regional liver directed therapy (cTACE, DEB-TACE and SIR-Spheres).

- Prior liver transplantation.

- Whole liver TheraSphere® treatment following prior liver resection.

- TheraSphere administration to ≤2 segments (e.g., radiation segmentectomy).

- Additional active therapy (TACE and treatment with SIR-Spheres) between first
TheraSphere treatment and 3 month (90 days) imaging.

- Hepatic vein invasion.

- Diagnosis of disease progression at peri-procedural imaging as compared to the
baseline imaging (physician's discretion).