Background: TACE induces a peripheral anti-tumor immune response, which may be amplified by immune checkpoint inhibitors (ICI). Combining TACE with dual ICI therapy has been shown to be safe and feasible. Recent data has suggested that Day-1 only anti-CTLA4 dosing, at a higher level of 300mg, could lead to a stronger immune response, and drive a greater expansion than lower dose regimens, whilst maintaining a tolerable safety profile. This novel schedule has not previously been combined with TACE. Methods: Patients with HCC (Childs Pugh A/B7, Barcelona clinic liver cancer stage B/C; ECOG 0/1; sorafenib-naive or experienced) were enrolled in a pilot study of tremelimumab at 2 dose levels (DL1: 75mg IV q4-weekly x 4 and DL2: 300mg IV D1 only) in combination with durvalumab (1500mg IV q-28d) and TACE (D36 +/- 96 hours) until progression of disease (per irRECIST) or off-study criteria. Peripheral immune monitoring was performed and tumor biopsies were obtained at time of TACE. Results: 13 patients enrolled on study; N = 3 at DL1 and N = 10 at DL2. M:F 10:3. Median age 70 (65-74). BCLC B/C 4/9. Extrahepatic disease 6/7. Aetiology: NASH (N = 3), alcohol-related disease (N = 1), HCV (N = 2), hemochromatosis (N = 1), unknown (N = 6). 1 pt discontinued due to G3 colitis. All patients evaluable for response with 2/10 pts on DL2 experiencing PR (at 8 weeks) and overall 7/13 SD and 1/13 PD as best response. Updated PFS and OS data to be presented. Conclusions: Tremelimumab (Day 1 only) and Durvalumab in combination with TACE is safe and feasible in patients with HCC. Follow-up is ongoing and full safety and efficacy data will be presented. Clinical trial information: 2019-002767-98.