Abstract 727TiP
Background
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.
Trial design
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.
Clinical trial identification
NCT05301842.
Editorial acknowledgement
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.
Legal entity responsible for the study
AstraZeneca.
Funding
AstraZeneca.
Disclosure
G.K. Abou-Alfa: Financial Interests, Personal, Advisory Board: Adicet, Alnylam, AstraZeneca, Autem, Beigene, Berry Genomics, Boehringer Ingelheim, Celgene, Cend, CytomX, Eisai, Eli Lilly, Exelixis, Flatiron, Genentech/Roche, Genoscience, Helio, Helsinn, Incyte, Ipsen, Merck, Nerviano, Newbridge, Novartis, QED, Redhill, Rafael, Servier, Silenseed, Sobi, Vector, Yiviva; Financial Interests, Personal, Other, IP License: PCT/US2014/031545 filed on March 24, 2014, and priority application Serial No.: 61/804,907; Filed: March 25, 2013; Financial Interests, Institutional, Research Grant: Arcus, AstraZeneca, BioNtech, BMS, Celgene, Flatiron, Genentech/Roche, Genoscience, Incyte, Polaris, Puma, QED, Silenseed, Yiviva; Non-Financial Interests, Principal Investigator: AstraZeneca, Yiviva, QED. J.P. Erinjeri: Financial Interests, Personal, Advisory Board: AztraZeneca. C.K. Kuhl: Financial Interests, Personal, Invited Speaker: Bayer, Bracco; Financial Interests, Personal, Advisory Board: Guerbet. R. Lencioni: Financial Interests, Personal, Other, Consulting fees: AstraZeneca, Bayer, Eisai, Roche. A. Zeng: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. B. Evans: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. G. Cohen: Financial Interests, Personal, Full or part-time Employment, I am a full time employee of AstraZeneca. Position is Global Clinical Lead in Immuno-oncology: AstraZeneca; Financial Interests, Personal, Stocks/Shares, Own stock in the company as an employee.: AstraZeneca. M. Kudo: Financial Interests, Personal, Invited Speaker: Eisai, Chugai, Eli Lilly, Bayer, Takeda, MSD; Financial Interests, Institutional, Research Grant: Otsuka, Sumitomo Dainippon Pharma, EA Pharma, Taiho, Eisai, AbbVie, Gilead Sciences, Takeda. All other authors have declared no conflicts of interest.