This pilot study evaluated the combination of pembrolizumab and Y90 radioembolization in patients with poor prognosis hepatocellular carcinoma (HCC). The study, conducted at three institutions, enrolled 29 patients, with 27 receiving at least one dose of both treatments. The primary endpoint was 6-month progression-free survival (PFS6), and secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability. Key findings include: - 15 out of 27 patients (55.6%) were progression-free at 6 months, with a median PFS of 9.95 months and a median OS of 27.30 months. - The ORR was 30.8%, and the disease control rate (DCR) was 84.6%. - Treatment was generally safe and tolerable, with common adverse events being grade 1 or 2. The study demonstrated that the combination of pembrolizumab and Y90 radioembolization showed promising efficacy and safety in patients with advanced, poor prognosis HCC, warranting further evaluation in larger, randomized trials.This pilot study evaluated the combination of pembrolizumab and Y90 radioembolization in patients with poor prognosis hepatocellular carcinoma (HCC). The study, conducted at three institutions, enrolled 29 patients, with 27 receiving at least one dose of both treatments. The primary endpoint was 6-month progression-free survival (PFS6), and secondary endpoints included time to progression (TTP), objective response rate (ORR), overall survival (OS), and safety/tolerability. Key findings include: - 15 out of 27 patients (55.6%) were progression-free at 6 months, with a median PFS of 9.95 months and a median OS of 27.30 months. - The ORR was 30.8%, and the disease control rate (DCR) was 84.6%. - Treatment was generally safe and tolerable, with common adverse events being grade 1 or 2. The study demonstrated that the combination of pembrolizumab and Y90 radioembolization showed promising efficacy and safety in patients with advanced, poor prognosis HCC, warranting further evaluation in larger, randomized trials.