ESMO Asia 2025 | Expanding immunotherapy options for hepatocellular carcinoma

For patients with AHCC, we have different options. For patients with advanced stage AHCC, we have different options represented by immunotherapy combinations. We have atezolizumab plus bevacizumab. We have durvalumab plus tremelimumab according to the STRIDE regimen. We have nivolumab plus ipilimumab. And of course, we still have tyrosine kinase inhibitors like lenvatinib and sorafenib, mostly lenvatinib. For patients without contraindications to immunotherapy, as I said, one of the immunotherapy combinations should be administered as a first-line treatment in the advanced setting. All these trials, all these combinations have been tested in trials, enrolling patients with very well-preserved liver function, Child-Pugh A, very good clinical conditions, ECOG performance status 0-1. And in most of the studies, except the IMbrave150 that tested the atezolizumab and bevacizumab, patients with main portal vein thrombosis were excluded. So there are patients that we see every day in clinical practice that have the characteristics based on which they would have not been enrolled in a clinical trial. So patients that cannot be treated in clinical practice with the standard of care. So we need to generate data. We need to expand the population that can be treated with immunotherapy combinations. And indeed, there is an ongoing phase 3B study, the Sierra study, that is testing STRIDE. That is the combination of a single primary dose of tremelimumab followed by durvalumab. And this regimen was tested in the phase 3 HIMALAYA study. And the combination was superior compared to sorafenib. So it was approved and is one of the standard of care. So this combination is being tested in the Sierra Phase 3B study, a single-arm study, that includes patients either with Child-Pugh B liver cirrhosis, B7 or B8, or patients with ECOG performance status 2, or patients with VP4, so main portal vein thrombosis. One of these factors. The study is still ongoing, but we have some data. The preliminary safety data were presented at ESMO-GI 2022, and some other safety data and the results in the Asian populations were presented at ESMO Asia 2022. The primary endpoint of the study are the possibly related adverse events of grade three and four and overall response rate. And what is clear from this study is that the adverse events observed in this population that is a less well-selected population compared to the HIMALAYA study, so compared to the population enrolled in a phase three study, the safety profile is quite similar. The adverse events, the immune-mediated adverse events, the use of steroids to manage the immune-mediated adverse events is very similar compared to what we have seen in the HIMALAYA study. And also the preliminary efficacy data presented at ESMO Asia in the Asian population are similar to what we have seen in the phase three trial in the HIMALAYA trial. So the studies are still ongoing, but if we will have the confirmation of this data in the whole population enrolled in the study, we will have the possibility to expand the use of STRIDE to a population that is less well selected compared to the population enrolled in the study and a population that is more similar to the population that we see every day in the clinic. So this is an important trial and we need to wait for the completion of the trial for the final analysis. But hopefully we will be able to treat more patients with the STRIDE regimen in clinical practice.

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