ABC-HCC: A phase IIIb, randomized, multicenter, open-label trial of atezolizumab plus bevacizumab versus transarterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma.

TPS498 Background: Hepatocellular carcinoma (HCC) is among the most common and deadliest cancers worldwide. In the intermediate stage the current standard of care is locoregional treatment with transarterial chemoembolization (TACE). The IMbrave150 phase 3 study has demonstrated that the combination of atezolizumab, an anti-PD-L1 antibody, and bevacizumab, an anti-VEGF antibody (atezo/bev), extends survival in comparison to sorafenib in the first-line setting in advanced HCC[1] which has led to its approval for patients with unresectable HCC. However, it is unknown whether atezo/bev is more efficacious than TACE for the treatment of intermediate HCC. ABC-HCC (NCT04803994) is a phase 3b, randomized, multicenter, open-label, investigator-initiated trial of atezo/bev versus TACE in intermediate stage HCC with high tumor burden exceeding the Milan criteria. Methods: The ABC-HCC study is recruiting patients ≥18 years of age who have a confirmed diagnosis of HCC in the intermediate stage (multifocal, exceeding the Milan criteria, no extrahepatic spread, no macrovascular invasion) and no curative treatment option. In addition, patients must have an ECOG performance status of 0, preserved liver function (Child-Pugh A), and ≥2 untreated lesions with a diameter > 10 mm and arterial hyperenhancement on cross-sectional imaging. Those who have previously received locoregional or systemic treatment are excluded. 434 patients will be randomly assigned 1:1 to systemic treatment (atezo at 1200 mg IV plus bev at 15 mg/kg IV) once every three weeks or to TACE. Both conventional and DEB-TACE are allowed. Region, AFP level (< 200 ng/mL vs. ≥200 ng/mL), and ALBI (1 vs. 2) will be used for stratification. Cross-sectional imaging (CT/MRI) will be performed every 8 weeks to determine the time to failure of treatment strategy, a novel primary endpoint. Failure of strategy is reached in case of progressive disease and any of the following: loss of clinical benefit, unacceptable toxicity, liver function deterioration, and therapy not further applicable for other reasons. Secondary endpoints are overall survival (OS), OS rate at 24 months, objective response rate, time to progression, time to loss of systemic treatment options, progression-free survival, duration of treatment, duration of response, time to deterioration of liver function, safety, and quality of life (EORTC QLQ-C30 and HCC18). Patients will be followed for survival, quality of life and subsequent anti-cancer therapy every 12 weeks after the end of study treatment. Recruitment for this study began in July 2021. FF, RK, JB and PRG contributed equally. References: 1. Finn RS, Qin S, Ikeda M, Galle PR, Ducreux M, Kim TY, et al. Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma. N Engl J Med. 2020;382(20):1894-905. doi: 10.1056/NEJMoa1915745. Clinical trial information: NCT04803994.