Clinical Summary: 

• Design/Population: The phase 3 EMERALD-3 trial evaluated STRIDE (single-dose tremelimumab plus durvalumab) with or without lenvatinib in combination with transarterial chemoembolization (TACE) in patients with embolization-eligible hepatocellular carcinoma.
• Key Outcomes: STRIDE-based regimens improved progression-free survival, objective response rates, and duration of response compared with TACE alone.
• Clinical Relevance: These findings support STRIDE-based therapy combined with TACE as a potential new treatment approach for patients with embolization-eligible hepatocellular carcinoma.

Results from the phase 3 EMERALD-3 trial demonstrated that combining STRIDE-based immunotherapy with transarterial chemoembolization (TACE), with or without lenvatinib, significantly improved progression-free survival (PFS) compared with TACE alone, supporting a potential new treatment strategy for patients with embolization-eligible hepatocellular carcinoma.

These results were presented by Joseph Erinjeri, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, at the ESMO Gastrointestinal Cancers Congress in Munich, Germany. 

In this international study, 760 patients were randomized 1:1:1 to receive STRIDE (300 mg of tremelimumab plus 1500 mg of durvalumab followed by 1500 mg of durvalumab every 4 weeks) plus lenvatinib (8 mg or 12 mg once daily) and TACE (n = 293), STRIDE plus TACE (n = 175), or TACE alone (n = 292). Treatment with durvalumab and lenvatinib continued for up to 36 months or until disease progression or discontinuation. The primary end point was blinded independent central review–assessed PFS by RECIST version 1.1. Key secondary end points included PFS by mRECIST, objective response rate (ORR), and duration of response.

Both STRIDE-based regimens improved PFS compared with TACE alone. At the first prespecified data cutoff, STRIDE plus lenvatinib and TACE reduced the risk of disease progression or death by 30% versus TACE alone (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.57-0.86; P = .0007). At the second prespecified analysis, STRIDE plus TACE also demonstrated a clinically meaningful PFS benefit (HR, 0.71; 95% CI, 0.56 to 0.91). Consistent improvements were observed by mRECIST, with hazard ratios of 0.64 (95% CI, 0.53 to 0.77) for STRIDE plus lenvatinib and TACE and 0.59 (95% CI, 0.46 to 0.75) for STRIDE plus TACE versus TACE alone.

The PFS benefit was accompanied by higher tumor response rates. By RECIST version 1.1, ORRs were 36.6% with STRIDE plus lenvatinib and TACE, 40.8% with STRIDE plus TACE, and 27% with TACE alone. Similar improvements were observed by mRECIST, with ORRs of 58.9%, 55.4%, and 41.7%, respectively.

Responses also appeared more durable with the STRIDE-based regimens. By RECIST version 1.1, median duration of response was 15.7 months with STRIDE plus lenvatinib and TACE, 18.4 months with STRIDE plus TACE, and 16.6 months with TACE alone. By mRECIST, corresponding median durations of response were 13.1 months, 14 months, and 10 months, respectively.

As Dr Erinjeri concluded, these results “further support a STRIDE-based regimen with TACE as a potential new treatment for [embolisation-eligible hepatocellular carcinoma]." 

Source: 

Erinjeri JP. Tumour response analyses by RECIST v1.1 and mRECIST in the phase III EMERALD-3 study of tremelimumab plus durvalumab with or without lenvatinib plus transarterial chemoembolisation (TACE) in embolisation-eligible hepatocellular carcinoma (eeHCC). Presented at ESMO GI. July 1-4, 2026; Munich, Germany, LBA2.