Durvalumab with or without Bevacizumab as Adjuvant Therapy for Patients with Hepatocellular Carcinoma at Risk of Recurrence After Curative Therapy: EMERALD-2

Purpose: Hepatic resection and ablation are standard of care for patients with hepatocellular carcinoma (HCC), but although potentially curative, the risk of recurrence is high (44%–79% at 5 years). No effective adjuvant therapy currently exists, and the prevention or delay of recurrence of HCC after curative treatment presents a high unmet medical need. Encouraging evidence suggests that adjuvant therapy involving agents that engage the immune response, including immunotherapy such as durvalumab (an anti–PD-L1 antibody), can prolong recurrence-free survival (RFS) in patients with early stage HCC. Additionally, vascular endothelial growth factor pathway inhibition may enhance activity of PD-L1 blockade in patients with HCC. EMERALD-2 (NCT03847428) is a phase 3 randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of durvalumab with or without bevacizumab as adjuvant therapy in patients at high risk of recurrence after curative resection or ablation.

Materials and Methods: Approximately 888 patients will be randomized 1:1:1 to arm A (durvalumab + bevacizumab), arm B (durvalumab + placebo), or arm C (placebo + placebo) after curative therapy. Stratification will be based on evidence of pathological microvascular invasion and geographic region. Eligible patients must have confirmed HCC, successfully completed curative therapy with imaging to confirm disease-free status 28 days before randomization, Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and Child-Pugh score of 5 or 6. Exclusion criteria include prior systemic anticancer therapy for HCC; known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC; metastatic, macrovascular invasion, or coexisting malignant disease at baseline; portal vein thrombosis; waiting for liver transplantation. Patients with hepatitis virus B or C (HBV, HCV) may be enrolled; HBV-positive patients must have adequate viral suppression before enrollment, and HBV or HCV replication will be monitored and treated if appropriate. The primary endpoint is RFS as assessed by blinded independent central radiology review using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Secondary endpoints include 2- and 3-year RFS, time to recurrence, overall survival, health-related quality of life, and safety.

Results: N/A

Conclusions: N/A