585 Background: The approval of atezolizumab + bevacizumab for untreated advanced HCC was a significant benefit for patients, but with an increased risk of potentially severe bleeding complications. Tivozanib (a selective VEGFR 1, 2, & 3 tyrosine kinase inhibitor [TKI]) has been combined with durvalumab in the DEDUCTIVE study; preliminary results presented in January 2022 showed that this combination was well tolerated with comparable efficacy to other immune checkpoint and VEGF containing regimens in patients with previously untreated HCC ( J Clin Oncol 40, no. 4 suppl 462-462). We now report the final results of this cohort (cohort A) of patients as well as those with previously treated HCC, including safety results for all the patients. Methods: Major eligibility criteria included age >18 yrs with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, and creatinine clearance >40 ml/min. Major exclusion criteria included co-infection with HBV and HCV and significant organ dysfunction. Patients were treated with 0.89 mg tivozanib p.o., 21 days on followed by 7 days off and 1500 mg durvalumab i.v. every 28 days. The primary objective was to determine the safety and tolerability of this combination in patients with advanced HCC; secondary objectives included assessing objective response rate (ORR), progression free survival, and overall survival (OS). The study was amended in 2021 to include a cohort of patients previously treated with atezolizumab and bevacizumab (cohort B). Results: 21 patients were enrolled in cohort A and 6 in cohort B; the median age was 67, 88% of patients were male, and 24% were Asian. The median follow-up time was 13.2 mos and 3.4 mos for cohorts A and B, respectively. Data were available for 25 of the 27 patients enrolled. For cohort A, the ORR was 25% (5/20) and 1-year OS was 76%. For safety analysis, 24 (96%) patients had at least 1 treatment-emergent adverse event (TEAE); 92% were attributed possibly to either tivozanib or durvalumab; 32% were serious TEAEs and there was 1 TEAE leading to death (unrelated). Of the 8 (32%) serious TEAE, 2 were coronavirus infection. 2 patients had serious (grade 3) treatment-related AEs: 1 pneumonitis and 1 with gastrointestinal hemorrhage and anemia. There were no grade 4 or 5 treatment-related AEs. Conclusions: Treatment with the combination of tivozanib and durvalumab in patients with either untreated advanced HCC or those previously treated with atezolizumab and bevacizumab was well tolerated; no severe bleeding events occurred in this study. Efficacy outcomes were comparable to other IO-TKI combinations in HCC. Data for PDL1 status, HBV/HCV status was collected and will be presented along with final safety and efficacy results for both cohorts. Clinical trial information: NCT03970616 .