1437 Analysis by treatment period and liver function in EMERALD-1: a phase 3 study of durvalumab ± bevacizumab + TACE in participants with embolization-eligible unresectable hepatocellular carcinoma

<h3>Background</h3> The Phase 3 EMERALD-1 study (NCT03778957) met its primary endpoint: durvalumab+bevacizumab+transarterial chemoembolization (TACE) significantly improved progression-free survival (PFS) versus placebo+TACE (HR, 0.77; 95% CI, 0.61–0.98; p=0.032) in participants with unresectable hepatocellular carcinoma (uHCC). Study regimen was administered in two phases, the durvalumab-TACE period and the durvalumab-bevacizumab period. This post hoc analysis assessed safety in both periods and efficacy by liver function. <h3>Methods</h3> Participants were randomized 1:1:1 to durvalumab+TACE, durvalumab+bevacizumab+TACE, or placebo+TACE. In the durvalumab-TACE period, participants received 1–4 TACE (number and modality per investigator choice) plus durvalumab (1500 mg) or placebo (Q4W). In the durvalumab-bevacizumab period, post-last TACE, participants received durvalumab (1120 mg) plus placebo, durvalumab (1120 mg) plus bevacizumab (15 mg/kg), or placebo (Q3W). Safety was assessed in the investigational product (IP)-treated set (participants who received any treatment in the arm to which they were randomized, until end of follow-up). PFS and time to progression (TTP) in the intent-to-treat population in the two study arms were assessed in participants with albumin-bilirubin (ALBI) Grade 1 or 2 at baseline (no participants had ALBI Grade 3 in the durvalumab+bevacizumab+TACE or placebo+TACE arms). <h3>Results</h3> Median duration of exposure to durvalumab or placebo for durvalumab was highest in the durvalumab+bevacizumab+TACE arm during the durvalumab-bevacizumab period. In the durvalumab+bevacizumab+TACE and placebo+TACE arms of the IP-treated set, adverse events were reported by 139 (72.0%) and 148 (74.0%) participants in the durvalumab-TACE period and 147 (76.2%) and 132 (66.0%) participants in the durvalumab-bevacizumab period (table 1); were possibly related to treatment in 56 (29.0%) and 41 (20.5%) participants in the durvalumab-TACE period and 114 (59.1%) and 69 (34.5%) participants in the durvalumab-bevacizumab period; and were provoked by TACE in 90 (46.6%) and 85 (42.5%) participants in the durvalumab-TACE period and 18 (9.3%) and 21 (10.5%) participants in the durvalumab-bevacizumab period, respectively. Incidence of adverse events with the outcome of death was low across treatment arms in both periods, with none reported with durvalumab+bevacizumab+TACE during the durvalumab-bevacizumab period. Regardless of ALBI Grade, baseline characteristics were generally consistent across treatment arms. In the intent-to-treat population, PFS and TTP were numerically improved with durvalumab+bevacizumab+TACE versus placebo+TACE regardless of baseline ALBI Grade (table 2). <h3>Conclusions</h3> Durvalumab+bevacizumab+TACE demonstrated a manageable safety profile across the durvalumab-TACE and durvalumab-bevacizumab periods, consistent with the individual agents and underlying disease. Numerical improvements in efficacy outcomes were observed with durvalumab+bevacizumab+TACE versus placebo+TACE, regardless of baseline ALBI Grade, supporting durvalumab+bevacizumab+TACE as a standard of care in embolization-eligible uHCC. <h3>Acknowledgements</h3> Medical writing support, under the direction of the authors, was provided by Derrick Bond, PharmD, CMC Connect, a division of IPG Health Medical Communications, and was funded by AstraZeneca, in accordance with Good Publication Practice (GPP 2022) guidelines. This abstract was originally submitted to the International Liver Cancer Association Annual Conference 2024. <h3>Trial Registration</h3> Clinical trial identification: NCT03778957. <h3>Ethics Approval</h3> The trial protocol was approved by local institutional review boards.