Key Clinical Takeaways:

• The multimodality regimen demonstrated encouraging antitumor activity, with high overall and disease control rates, including a notable proportion of complete responses and successful conversion to surgical resection in select patients.
• Durable clinical benefit was observed in some patients, with long-term remissions following hepatectomy and sustained survival outcomes despite high-risk disease features.
• Treatment was feasible and generally well tolerated, with a manageable safety profile, no treatment-related deaths, and adverse events consistent with the known profiles of the component therapies.

Farshid Dayyani, MD, PhD, University of California, Irvine, California, discusses results from 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 1, 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’m here to summarize the data presented at the ASCO GI Conference in 2026, where we presented this single-arm, 2 institution, open-label, phase 2 investigational trial in patients with liver-limited unresectable HCC.

Our presentation included a total of 24 patients. The median age was 67 years; 83% were male; 58% were Asian; 21% were non-Hispanic White; and 17% were Hispanic. Thirty-three percent had hepatitis B, 25% had hepatitis C, and 42% had other etiologies. Child-Pugh B7 was present in 12% of patients, and the rest had Child-Pugh A scores of 5 or 6. Importantly, 58%, or almost 60%, of patients had received prior locoregional therapy. Systemic treatment was excluded. 

An important takeaway regarding completion of locoregional treatment was that all patients completed the planned TACE. In terms of treatment-related adverse events, all grade treatment-related adverse events included hand-foot syndrome, or PPE, in 29%, hypothyroidism in 25%, and diarrhea, pruritus, and AST elevation each in 17%. Nine patients, or 38%, experienced grade 3/4 treatment-related adverse events. Importantly, there were no grade 5 adverse events in this study.

In terms of efficacy, the median progression-free survival was 6.3 months. Median overall survival in this population was 13 months and was not yet mature. Progression-free survival at 6months was 55% in this population. In terms of response by mRECIST, the overall response rate and disease control rate were 61% and 89%, respectively, which represents a relatively high overall response rate, including partial and complete responses. Five patients, or 28%, achieved a complete response by mRECIST. Importantly, 2 patients with fairly large tumors at baseline—14 cm and 13 cm—were able to undergo curative-intent hepatectomy after 7.6 months and 4.6 months, respectively, on protocol treatment. These patients were observed after resection and remained without evidence of disease approximately 40 months after surgery. Pathologic assessment at the time of resection showed 100% necrosis in 1 patient and 80% necrosis in the other.

The implications of these findings are that we demonstrated encouraging activity in a real-world population of patients with advanced, liver-limited HCC that extended beyond traditional trials such as EMERALD-1 or LEAP-012, where prior locoregional therapy was excluded and only Child-Pugh A patients were allowed. In our study, 60% of patients had prior locoregional therapy, and Child-Pugh B7 disease was present in about 12% of patients. Despite this, we observed an encouraging overall response rate of 61%, with conversion to resection in a subset of patients who remain disease-free, and a manageable safety profile with no new safety signals.

While enrollment is ongoing, we are already considering how to incorporate these findings into the next generation of trials. Over the past 5 to 6 years, transarterial radioembolization with Y-90 has shown high efficacy in HCC and liver-limited HCC, with high response rates, and has been de facto adopted by many academic institutions. We learned that upfront systemic induction for a slightly longer duration than a single dose may be beneficial to further debulk the tumor prior to locoregional consolidation. Overall, it is encouraging that dual immune checkpoint blockade can be combined with a small-molecule inhibitor, or TKI, and integrated with locoregional consolidation in these patients with promising results.

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