Clinical Summary: 

• Design/Population: The phase 3 EMERALD-3 trial evaluated STRIDE (tremelimumab plus durvalumab) with or without lenvatinib combined with transarterial chemoembolization (TACE) versus TACE alone in patients with unresectable hepatocellular carcinoma eligible for embolization.
• Key Outcomes: STRIDE plus TACE significantly improved progression-free survival compared with TACE alone. Early overall survival analyses showed favorable trends, although survival data remain immature. Addition of lenvatinib did not improve outcomes compared with STRIDE plus TACE alone.
• Clinical Relevance: These findings support integration of immunotherapy with embolization and suggest that STRIDE plus TACE may represent a new treatment standard for patients with embolization-eligible hepatocellular carcinoma.

Ghassan Abou-Alfa, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, discusses results from the EMERALD-3 trial evaluating immunotherapy-based strategies combined with transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma. The study assessed whether adding STRIDE alone or STRIDE plus lenvatinib to TACE could improve outcomes compared with embolization alone.

The trial demonstrated a significant progression-free survival benefit with STRIDE plus TACE, while overall survival curves already favor the immunotherapy-containing arms despite limited maturity of the data. Importantly, the addition of lenvatinib did not appear to provide meaningful benefit beyond STRIDE plus TACE, supporting a simplified treatment approach that may be readily incorporated into clinical practice.

Dr Abou-Alfa presented these results at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.

Transcript:

On behalf of all my coauthors, it was a great delight to present the EMERALD-3 study. As you heard, this study evaluated the combination of tremelimumab plus durvalumab, or what is known as the STRIDE regimen, together with chemoembolization.

It was really exciting to see this concept that we have been discussing for some time. As you know, with chemoembolization, we release tumor antigens and potentially activate immune pathways. This creates a great opportunity to add checkpoint inhibitors, including the anti–PD-L1 antibody durvalumab, further enhanced by adding lenvatinib as an anti-VEGF agent, and, at the top of the chain, the anti–CTLA-4 antibody tremelimumab.

The study had 3 arms: Arm A was the STRIDE regimen plus lenvatinib plus chemoembolization, Arm C was chemoembolization alone. The primary end point was progression-free survival. We also looked at overall survival as a secondary end point for Arm A compared with Arm C. In addition, Arm B consisted of STRIDE plus chemoembolization without lenvatinib, compared with Arm C. Again, we evaluated both progression-free survival and overall survival. 

We were delighted to present data on all four of these end points. However, the progression-free survival analysis for Arm A versus Arm C was the only end point that was sufficiently mature for formal analysis. The other end points were analyzed as well, but overall survival maturity was only about 40% to 45%. Even so, we are already seeing trends favoring the STRIDE-containing arms.

An important point that came up during the discussion was the comparison between Arm A and Arm B—that is, STRIDE plus lenvatinib plus chemoembolization versus STRIDE plus chemoembolization alone. The good news is that this was a prespecified analysis within the study. There was essentially no difference between the two groups. Whether lenvatinib was added or not did not appear to matter.

There was only 1 subgroup—the Japanese population, which represented a relatively small proportion of patients, about 7.5%—where there appeared to be a potential advantage with the addition of lenvatinib. However, for the broader global population, it appears that STRIDE plus chemoembolization alone was sufficient to achieve the improvement in progression-free survival.

As I mentioned, the overall survival curves are already clearly separating. It is likely only a matter of time before the data mature enough to confirm this statistically. Regarding adverse events, there were no major surprises. We observed the expected toxicities associated with chemoembolization, including post-embolization syndrome, as well as the expected immune-related adverse events associated with the STRIDE regimen. Importantly, the main reason for treatment discontinuation in Arm A was lenvatinib toxicity. Approximately 78% of discontinuations were related to lenvatinib-associated adverse events, primarily hypertension.

So what happens after ASCO– the good news is that all of these agents are already approved and available, which simplifies implementation. I believe we now have sufficient evidence to move forward and consider that, for patients who are candidates for chemoembolization, adding the STRIDE regimen is an appropriate strategy. 

The timing is important, the STRIDE regimen should be initiated within 7 days of the start of chemoembolization. This consists of 1 dose of tremelimumab, 1 dose of durvalumab, chemoembolization, and then continuation of durvalumab on a monthly basis. Thank you very much for listening, and have a great day.

Source: 

Abou-Alfa G, Ren Z, Erinjeri JP, et al. Efficacy and safety results from EMERALD-3: A phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. LBA4000.