mRECIST Outcomes in EMERALD-1: A Phase 3, Randomized, Placebo-Controlled Study of Transarterial Chemoembolization plus Durvalumab with or without Bevacizumab in Participants with Embolization-Eligible Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) is a standard of care for embolization-eligible unresectable hepatocellular carcinoma (uHCC); however, most people with uHCC treated with TACE progress within one year. The primary endpoint of the Phase 3 EMERALD-1 study (NCT03778957) was positive, with a statistically significant improvement in progression-free survival (PFS) assessed by blinded independent central review (BICR) per RECIST v1.1 with durvalumab (D) + bevacizumab (B) + TACE versus TACE (Table). In addition to RECIST v1.1, efficacy of the regimens was assessed using modified RECIST (mRECIST). The hypothesis was that PFS improvement with D + B + TACE versus TACE was consistent, as assessed per mRECIST and RECIST v1.1. Embolization-eligible participants (pts) were randomized 1:1:1 to receive D + B + TACE, D + TACE, or TACE (cTACE or DEB-TACE per investigator choice). Pts received D (1500 mg) or placebo for D (Q4W) plus TACE. After completion of last TACE, pts received D (1120 mg) plus placebo for B, D (1120 mg) plus B (15 mg/kg), or placebos for D and B (Q3W). PFS was assessed by BICR and the investigator per mRECIST as a secondary endpoint. PFS improved with D + B + TACE versus TACE as assessed by BICR and the investigator per mRECIST (Table). The estimation of effect was consistent with that of the primary endpoint, which showed a statistically significant improvement in PFS with D + B + TACE versus TACE, as assessed by BICR per RECIST v1.1 (p = 0.032, significance threshold 0.0435; Table). D + TACE versus TACE showed similar PFS results as assessed per mRECIST and RECIST v1.1 (Table). D + B + TACE is the first immune checkpoint inhibitor-based regimen in a global Phase 3 trial to show statistically significant improvement in PFS versus TACE in pts with embolization-eligible uHCC, as assessed by BICR per RECIST v1.1, with consistent PFS results, as assessed per mRECIST. These results further support the potential for D + B + TACE to set a new standard of care in uHCC. [ABSTRACT FROM AUTHOR]