Transarterial Chemoembolization with Durvalumab or Durvalumab + Bevacizumab in Patients with Locoregional Hepatocellular Carcinoma: EMERALD-1

Purpose: Because curative therapy is not always feasible and there is no standard systemic therapy, patients with intermediate-stage hepatocellular carcinoma (HCC) are treated with locoregional therapy such as transarterial chemoembolization (TACE). TACE therapy achieves tumor responses, but recurrence is common and often occurs within 1 year. Early evidence shows encouraging activity and durable clinical response for checkpoint inhibitors (CIs), such as durvalumab, as treatment for advanced HCC and when combined with TACE. CIs combined with vascular endothelial growth factor (VEGF) inhibitors also show promise in patients with advanced HCC. Taken together, combining durvalumab, VEGF inhibitors, and TACE therapies warrants evaluation in patients with locoregional HCC. EMERALD-1 (NCT03778957) is a randomized, double-blind, placebo-controlled, multicenter phase 3 study assessing the efficacy and safety of durvalumab monotherapy when given with either drug-eluting bead (DEB)-TACE or conventional TACE (cTACE) followed by durvalumab ± bevacizumab in patients with HCC not amenable to curative therapy.
 

Materials and Methods: A total of 600 patients will be randomized 1:1:1 to arm A (DEB-TACE or cTACE + durvalumab and followed by durvalumab + placebo), arm B (DEB-TACE or cTACE + durvalumab followed by durvalumab + bevacizumab), or arm C (DEB-TACE or cTACE + placebo). Durvalumab therapy will begin 7 days after the initial TACE procedure. Durvalumab ± bevacizumab will begin 14 days after the last TACE procedure. Eligible patients must have confirmed HCC not amenable to curative therapy, Child-Pugh score A to B7, and Eastern Cooperative Oncology Group (ECOG) performance status of 0/1. Patients with a history of nephrotic or nephritic syndrome, clinically significant cardiovascular disease, extrahepatic disease, or main portal vein thrombosis (Vp3/Vp4) are excluded. Patients with active (controlled) or past hepatitis virus B or C infection may be enrolled. The primary endpoint is progression-free survival (PFS) for arm A versus arm C by blinded independent radiology review using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints include PFS for arm B versus arm C, overall survival, health-related quality of life, and safety.

Results: N/A Conclusions: N/A