IKF-035/ABC-HCC: A phase IIIb, randomized, multicenter, open-label trial of atezolizumab plus bevacizumab versus transarterial chemoembolization (TACE) in intermediate-stage hepatocellular carcinoma.

Abstract

478 Background: Hepatocellular carcinoma (HCC) is among the most common and deadliest cancers worldwide. Locoregional treatment (LRT) with transarterial chemoembolization (TACE) is standard of care (soc) for intermediate stage (BCLC B) HCC. The IMbrave150 phase 3 study demonstrated that combination of the anti-PD-L1 antibody atezolizumab and the anti-VEGF antibody bevacizumab (atezo/bev) extends survival compared to sorafenib in first-line treatment of advanced and intermediate stage HCC failing/unsuited for TACE which has led to its approval in this setting. However, it is unknown if atezo/bev is more efficacious than TACE in patients with intermediate stage HCC patients who would be treated with TACE per soc. While several trials assess the benefit of adding systemic therapy to TACE vs. TACE alone, the ABC-HCC trial directly compares the efficacy and safety of systemic treatment with atezo/bev vs. TACE. ABC-HCC is using a group sequential design with two planned interim analyses (IA) at 33% and 66% information time to assess efficacy/futility. Methods: ABC-HCC is an international phase 3b, randomized, multicenter, open-label, investigator-initiated trial directly comparing atezo/bev vs. TACE in intermediate stage HCC or HCC with indication for TACE according to the treating physician. 320 patients with confirmed HCC (not amenable to curative surgery/ablation, liver transplantation, but amenable to TACE, no extrahepatic spread, no macrovascular invasion except for Vp1/2, ECOG ≤ 1, Child-Pugh A/B7) are randomized (1:1) to receive either systemic treatment (Arm A: atezo, 1,200 mg IV; bev, 15 mg/kg IV; Q3W; max. 24 months) or TACE (Arm B: on demand as long as TACEable as assessed by the investigator). Imaging (CT/MRI) is performed Q8W to determine the primary endpoint time to failure of treatment strategy (TTFS: Time from randomization until death or need for a further therapeutic option). Here, we report on the first efficacy/futility IA at 33% information time (85 events). Results: To date, 206 pts have been enrolled at 54 centers in Austria, France, Germany, India, Italy, Japan and Spain. At data cut-off (06/13/2025), 194 pts were randomized, of whom 168 pts had a follow up duration of ≥ 3 months and were included in the IA (Arm A: 87; Arm B: 81). 100 events were observed for the primary endpoint TTFS (Arm A: 44; Arm B: 56). Median TTFS was 14.6 months in Arm A vs. 9.5 months in Arm B with a HR of 0.55 (95% CI [0.36, 0.83]). Based on these results, the trial was continued. Conclusions: The results of the first IA provide important insights into the efficacy of atezo/bev vs. TACE in intermediate stage HCC and suggest a superiority of systemic therapy compared to TACE in regard to TTFS. Based on these findings, the trial is progressing to the second IA at 66% information time (169 events). Clinical trial information: 2024-512953-26-00 .