CIO 2022-1 Transarterial Chemoembolization ± (Tremelimumab and Durvalumab ± Lenvatinib) in Hepatocellular Carcinoma: EMERALD-3

Purpose: Locoregional therapies such as transarterial chemoembolization (TACE) are the most common treatments for patients with intermediate-stage hepatocellular carcinoma (HCC). Although TACE results in tumor responses, progression and recurrence are common, and the median overall survival (OS) period is approximately 20 months. TACE may alter the tumor microenvironment and serve as a primer for immunotherapies. The STRIDE regimen of single tremelimumab (high, priming 300-mg dose) regular-interval durvalumab (1500 mg every 4 weeks) improved OS versus sorafenib in patients with unresectable HCC.1 Lenvatinib improved survival outcomes versus TACE in patients with unresectable HCC in a proof-of-concept study.2 EMERALD-3 (NCT05301842) is a phase 3, randomized, open-label, sponsor-blind, multicenter study assessing the efficacy and safety of STRIDE with or without lenvatinib given concurrently with TACE (either drug-eluting bead TACE or conventional TACE) versus TACE alone in patients with intermediate-stage HCC not amenable to curative therapy.

Materials and Methods: A total of 525 patients will be randomized 1:1:1 to arm A (STRIDE plus lenvatinib [8 mg or 12 mg] once daily plus TACE), arm B (STRIDE plus TACE), or arm C (TACE alone). In arms A and B, the first TACE procedure will occur no earlier than 7 days after tremelimumab and the first dose of durvalumab (and lenvatinib in arm A). In arm C, the first TACE procedure will occur within 7 days after randomization. Eligible patients must have confirmed HCC (by imaging or histopathology) not amenable to curative therapy but eligible for embolization, Child-Pugh score class A, Eastern Cooperative Oncology Group performance status of 0 to 1, measurable disease by modified Response Evaluation Criteria in Solid Tumors (mRECIST), and adequate organ and marrow function. Patients with visible baseline major portal vein invasion (Vp3/Vp4) or uncontrolled hypertension are excluded. The primary endpoint is progression-free survival (PFS) for arm A versus arm C by blinded independent review using RECIST v1.1. Additional endpoints include PFS for arm B versus arm C, OS, health-related quality of life, and safety.

Results: This trial is in progress.

Conclusions: This trial is in progress.