In ESMO GI 2025 I have presented the SIERRA study on behalf of the study team. It’s a phase IIIb study to look at the first-line use of tremelimumab and durvalumab, known as the STRIDE regimen, in HCC patients with adverse prognostic features.

What was the study design?

The objective of the clinical trial is to study the safety and also efficacy of the STRIDE regimen in those populations with poor prognostic features. The reason is because these populations are usually excluded by phase III clinical trials but there are actually a lot of patients, for example, with poor liver function, suboptimal performance status or the main portal vein thrombosis. This group is certainly an unmet need.

So this study is a single arm, open label, and all patients will be treated with the STRIDE regimen until progressive disease or toxicity or withdrawal of consent. The primary endpoints are both overall response rate and also the AE, the adverse events, related to the study treatment, grade 3-4 within six months of the administration of the STRIDE regimen.

What were the results?

The key results of the SIERRA IIIb study is that we presented the first endpoint which is the adverse events grade 3-4, possibly related to the study treatment within the first six months of time.  This study found around 19.1% of the patients have these grade 3-4 AEs related to treatment within six months. However, the chance of discontinuation of the treatment or even death from the adverse events are very low, lower than 4% and 2% respectively. Regarding those patients who required steroids for the treatment AEs, actually it’s lower than 20% and around 11% required high-dose steroids.

So based on the presentation, we showed that safety-wise it was quite reasonable and well tolerated in this group of patients with poor prognostic features when they are having treatment with the STRIDE regimen for cancer treatment.

What is the clinical significance of these results, and what is next for this study?

The significance is that in the old days we didn’t have any treatment for these patients with a poor prognosis because, as mentioned, they were usually excluded from the clinical trials. So this time we showed that at least it’s safe, based on the safety analysis in the SIERRA IIIb study. The next step is to look at the efficacy, the response, the survival and also the quality of life of the populations. In the future it opens an opportunity to look at the use of safer regimens, in this case the STRIDE regimen, in patients with poor prognostic features.