727TiP A randomised phase III study of tremelimumab (T) plus durvalumab (D) with or without lenvatinib combined with concurrent transarterial chemoembolisation (TACE) versus TACE alone in patients (pts) with locoregional hepatocellular carcinoma (HCC): EMERALD-3

Abstract

Locoregional therapies such as TACE are the most common treatments for pts with intermediate-stage HCC. Although TACE results in tumour responses, progression and recurrence are common, and median overall survival (OS) is approximately 20 months. TACE may alter the tumour 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 vs sorafenib in pts with unresectable HCC (Abou-Alfa et al. J Clin Oncol 2022;40(suppl 4). Abs 379). Lenvatinib improved survival outcomes vs TACE in patients with unresectable HCC in a proof of concept study (Kudo et al. Cancers [Basel] 2019;11:1804). EMERALD-3 (NCT05301842) is a phase III, randomised, open-label, sponsor-blind, multicentre study assessing the efficacy and safety of STRIDE, with or without lenvatinib, given concurrently with TACE (either drug-eluting bead TACE or conventional TACE) vs TACE alone in pts with intermediate-stage HCC not amenable to curative therapy. 525 pts will be randomised 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 Arm A and Arm B, the first TACE procedure will occur no earlier than 7 days following T and the first dose of D (and lenvatinib in Arm A); in Arm C the first TACE procedure will occur within 7 days post-randomisation. Eligible pts must have confirmed HCC (by imaging or histopathology) not amenable to curative therapy but eligible for embolisation, Child-Pugh score class A, Eastern Cooperative Oncology Group performance status of 0 to 1, measurable disease by modified Response Evaluation Criteria In Solid Tumours (mRECIST) and adequate organ and marrow function. Pts 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 vs Arm C by blinded independent review using RECIST v1.1. Additional endpoints include PFS for Arm B vs Arm C, OS, health-related quality of life and safety. NCT05301842. Medical writing support, under the direction of the authors, was provided by Brian Woolums, PhD, of CMC Connect, McCann Health Medical Communications, with funding from AstraZeneca, in accordance with Good Publications Practice (GPP3) guidelines. AstraZeneca.