Key Clinical Takeaways:

• This phase 2 study evaluates a multimodality strategy for liver-limited unresectable hepatocellular carcinoma that integrates induction immunotherapy, transarterial chemoembolization, and consolidation systemic therapy.
• The trial included patients with high-risk features, such as portal vein branch thrombosis, prior locoregional therapy, and underlying liver dysfunction, addressing an unmet clinical population.

Farshid Dayyani, MD, PhD, University of California, Irvine, California, discusses the background and methods of a phase 2 study evaluating a multimodality treatment strategy combining immunotherapy, transarterial chemoembolization, and targeted therapy in patients with liver-limited unresectable hepatocellular carcinoma, including those with high-risk features.

This study was presented at the 2026 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium in San Francisco, California.

For Part 2, please click here.

Transcript: 

My name is Dr Farshid Dayyani, I’m a professor of clinical medicine at the Chao Family Comprehensive Cancer Center at the University of California, Irvine. I would like to briefly discuss our clinical trial of ipilimumab and nivolumab in combination with TACE, followed by cabozantinib and nivolumab consolidation in patients with unresectable hepatocellular carcinoma (HCC) which was presented recently at ASCO GI 2026 as Abstract 542.

The background of the study, which we initiated in 2019, was recognizing the complex involvement of angiogenesis, the tumor microenvironment, and the new tools that were emerging, including next-generation small-molecule inhibitors, RTK inhibitors, as well as checkpoint inhibitors. We recognized the possibility of modulating the tumor microenvironment using dual checkpoint inhibition with ipilimumab and nivolumab to prime the tumor microenvironment, then treating the tumors within the liver with transarterial chemoembolization (TACE) which was standard about 6 or 7 years ago, and then attempting to consolidate that response with cabozantinib, which is a MET, AXL, and VEGF receptor tyrosine kinase inhibitor, plus nivolumab, an anti-PD-1 agent. 

The primary objective of this phase 2 trial was to estimate the efficacy of cabozantinib combined with ipilimumab and nivolumab priming and TACE in unresectable HCC. We had dual primary end points of progression-free survival at six months as well as complete response rate by mRECIST, along with standard secondary objectives of efficacy, safety, and tolerability. The study design included patients with liver-limited unresectable HCC diagnosed histologically or by radiographic criteria, Child-Pugh score A through B7, with albumin allowed. Patients were not candidates for resection or transplantation, were older than 18 years of age, had a performance status of 0 to 2, and had at least 1 measurable lesion. Importantly, prior locoregional treatment was allowed as long as it was completed more than 3 months prior to enrollment in the study. This resulted in a much more real-world patient population. As long as patients were eligible for TACE at the time of enrollment, vascular invasion was allowed.

The main exclusion criterion was extrahepatic metastatic disease, but otherwise any liver-limited patient was allowed to enroll in the trial. The design involved priming patients with 1 dose of ipilimumab at 1 mg/kg plus nivolumab at 3 mg/kg. Three weeks after this initial priming dose, patients underwent a TACE procedure, with the specific technique determined by the treating interventional radiologist. TACE was allowed to be repeated up to 2 additional times as needed, every 14 days. After completion of TACE, patients were started on consolidation therapy with cabozantinib 40 mg daily on a continuous basis, plus nivolumab 480 mg as a fixed dose once a month. Cabozantinib dose reductions were allowed based on adverse events, with 2 additional dose reduction levels: the first reduction to 20 mg daily, and the second reduction to 20 mg every other day.

We reached the prespecified interim analysis and the futility end point, and therefore decided to summarize the data at the ASCO GI Conference in 2026.

Source: 

Dayyani F, Valerin JB, Fernado D, et al. Phase 2 study of cabozantinib (Cabo) combined with ipilimumab (Ipi)/nivolumab (Nivo) and transarterial chemoembolization (TACE) in patients with liver limited unresectable hepatocellular carcinoma (uHCC).Presented at ASCO Gastrointestinal Cancers Symposium. January 8 - 12, 2026; San Francisco, California. Abstract 543