Regorafenib and Yttrium-90 Radioembolization for Unresectable Hepatocellular Carcinoma

Participants will orally self-administer Regorafenib tablets for the first 21 days of each 28-day cycle as follows. Dose-escalation will occur only if there are no significant drug-related adverse events: * Safety Run-in Phase: For the first six (6) participants enrolled. The starting dose is 80 mg/day during Cycles 1 and 2. In Cycle 3, the starting dose is 80 mg/day on Days 1 to 7, escalating to 120 mg/day on Days 8 to 14, and then escalating to a maximum dose of 160 mg/day on Days 15 to 21. Participants will continue to receive the maximum tolerated dose determined at the end of Cycle 3. * Phase 2: For participants enrolled after the Safety Run-in phase. In Cycle 1, the starting dose is 80 mg/day on Days 1 to 7, escalating to 120 mg/day on Days 8 to 14, and then escalating to a maximum dose 160 mg/day on Days 15 to 21. From Cycle 2 onward, participants will take 160 mg/day (or maximum tolerated dose from Cycle 1), on Days 1 to 21.

Y-90 absorbed glass microspheres will be administered standard of care once via the percutaneous trans-arterial approach after the first 3 weeks of Regorafenib treatment but before Day 28. Additional Y-90 absorbed glass microsphere administration is allowed for treatment of baseline disease in the absence of disease progression within 6 months of the initial Y-90 TARE treatment.