Atezolizumab Combo May Improve Outcomes Vs TACE in Intermediate-Stage HCC

Systemic therapy with atezolizumab (Tecentriq) plus bevacizumab (Avastin) may show superior outcomes compared with transarterial chemoembolization (TACE) among patients with intermediate-stage hepatocellular carcinoma (HCC), according to a presentation of interim analysis findings from the phase 3b IKF-035/ABC-HCC trial (NCT04803994) at the 2026 ASCO Gastrointestinal Cancers Symposium.

Data showed a median time to failure of treatment strategy (TTFS) of 14.59 months (95% CI, 11.07-17.97) among 87 patients who received atezolizumab/bevacizumab vs 9.46 months (95% CI, 6.97-11.27) among 81 of those who received TACE (HR, 0.545; 95% CI, 0.359-0.826; P = .0043). With a data cutoff of June 13, 2025, the investigators noted that data from the interim analysis were still premature and based on specific site reporting. Additionally, data cleaning is underway, with a potential for slight changes at the time of the final analysis.

In arm A, 97.7% of patients completed at least 1 dose of atezolizumab plus bevacizumab, with a median of 12 (range, 1-32) dosing cycles. In arm B, 93.8% of patients received at least 1 dose of TACE; the median number of TACE cycles was 2 (range, 1-8).

“This is a first interim analysis of the comparison of systemic therapy with [atezolizumab/bevacizumab] vs TACE in patients with intermediate-stage disease. We see nothing unexpected with respect to safety, but [there were slightly] more safety events in arm A,” presenting study author Peter Galle, MD, PhD, Chairman of the First Department of Internal Medicine at University Medical Center in Mainz, Germany, stated. “Based on these positive data, this trial continues.”

According to Galle, the second interim analysis at 66% information times is expected to occur in the third quarter of 2026.

Investigators of the international, multicenter, open-label phase 3b trial are evaluating the safety and efficacy of atezolizumab/bevacizumab vs TACE among patients with intermediate-stage HCC. An estimated population of 320 patients will be randomly assigned 1:1 to receive atezolizumab at 1200 mg intravenously plus bevacizumab at 15 mg/kg every 3 weeks (n = 160) or TACE.

The trial’s primary end point is TTFS. For patients receiving atezolizumab/bevacizumab in arm A, this encompasses radiologic progression plus any of the following: the loss of clinical benefit, unacceptable toxicity, liver function deterioration, or therapy becoming inapplicable for other reasons. In arm B, those who experience radiologic progression or stable disease on TACE fulfill the criteria for TTFS.

Secondary end points of the trial include overall survival, objective response rate, time to progression, time to loss of systemic treatment, progression-free survival, duration of response, and safety. Additionally, investigators will evaluate baseline PD-L1 protein expression in FFPE tumor tissue as an exploratory end point.

Patients with intermediate-stage HCC that is not amenable to curative surgery, liver transplantation, or curative ablation but amenable to TACE are eligible for enrollment on the trial. Other eligibility criteria include having a Child-Pugh-Score of A or B7, no extrahepatic disease, no massive multinodular pattern preventing adequate TACE, an ECOG performance status of 0 or 1, and no other severe comorbidities.

Investigators are conducting the study at approximately 70 studies across Germany, Spain, France, Italy, Austria, Japan, and India. As of December 2025, 231 patients have enrolled on the study.

At the time of analysis, the median age was 73 years (range, 51-89) in the atezolizumab arm and 73 years (range, 45-88) in the TACE arm, with most patients from each arm being male (86.2% vs 84.0%). Additionally, most patients in each respective arm had an ECOG performance status of 0 (81.6% vs 93.8%), a BCLC status of B (59.8% vs 77.8%), and no minimal vascular invasion (90.8% vs 96.3%).

Of note, 8.0% of patients in arm A experienced toxicity without progressive disease. In arms A and B, respectively, 9.2% vs 3.7% of patients reached the maximum treatment duration after 24 months.

All patients (100%) experienced at least 1 adverse effect (AE) across both arms, with 55.2% from arm A and 40.7% from arm B having grade 3 or higher toxicities. Any-grade serious AEs (SAEs) were reported in 44.8% and 35.8% of patients in each respective arm; 18.4% and 13.6% had grade 3 or higher SAEs. Additionally, 6.9% and 5.2% of patients experienced fatal SAEs, which included 1 patient in arm A (1.1%) who had an event related to study treatment.

The most common AEs in each respective arm included hypertension (26.4% vs 9.9%), diarrhea (24.1% vs 8.6%), anorexia (16.1% vs 6.2%), weight loss (14.9% vs 6.2%) and pruritus (12.6% vs 4.9%).

Disclosures: Galle noted receiving honoraria from Adaptimmune; AstraZeneca/MedImmune; Bayer Schering Pharma; Bristol-Myers Squibb; Ipsen; MSD; Roche/Genentech; Sirtex Medical. He also cited consulting or advisory roles with Adaptimmune; Bayer Schering Pharma; Boston Scientific; Bristol-Myers Squibb; Lilly; MSD; Roche/Genentech; and Sirtex Medical. He noted Speakers’ Bureau roles with AstraZeneca; Bayer Schering Pharma; BMS GmbH & Co. KG; Ipsen; Lilly; and Roche. Additionally, he also highlighted researching funding from Roche/Genentech as well as Travel and Accommodations Expenses from AstraZeneca; Bayer Schering Pharma; Lilly; Roche/Genentech; Sirtex Medical.

Reference

Galle PR, Bruix J, Kloeckner R, et al. 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. J Clin Oncol. 2026;44(suppl 2):478. doi:10.1200/JCO.2026.44.2_suppl.478