Durvalumab/Tremelimumab Combo Improves PFS in Unresectable HCC

The combination of durvalumab (Imfinzi) and tremelimumab (Imjudo), administered as the STRIDE regimen, plus lenvatinib and transarterial chemoembolization (TACE) demonstrated a statistically significant improvement in progression-free survival (PFS) vs TACE alone in patients with embolization-eligible unresectable hepatocellular carcinoma (HCC), meeting the primary end point of the phase 3 EMERALD-3 trial (NCT05301842).¹

At a prespecified interim analysis, the regimen also showed a trend toward improvement in overall survival (OS), though formal OS testing was not conducted at this time point.

AstraZeneca reported that full data from EMERALD-3 will be presented at a forthcoming medical meeting, and they have shared results with global regulatory authorities.

“Dual immunotherapy with durvalumab and tremelimumab in the STRIDE regimen represents a meaningful advance for patients with embolization-eligible liver cancer, who currently lack systemic treatment options to keep their cancer from progressing or recurring, with a trend of improving survival. EMERALD3 shows we can now significantly reduce the risk of disease progression with STRIDE as the immunotherapy backbone alongside lenvatinib and TACE,” Ghassan Abou-Alfa, MD, JD, MBA, PhD(hc), principal investigator of EMERALD-3, as well as an attending physician and professor of medicine at Memorial Sloan Kettering Cancer Center in New York, New York, stated in a news release.¹

EMERALD-3 Design and Patient Population

EMERALD-3 is an open-label, sponsor-blinded, global multicenter trial designed to examine whether adding a single priming dose of tremelimumab (300 mg) to durvalumab (1500 mg), then continuing durvalumab every 4 weeks alongside TACE, with or without lenvatinib (Lenvima), offers an advantage over TACE alone.^1,2 Patients were adults aged 18 to 120 who presented with locoregional HCC that could not be treated curatively yet remained appropriate for TACE. To qualify, patients also needed to show no extrahepatic spread, Child-Pugh class A liver function, an ECOG performance status of 0 or 1, disease measurable by mRECIST, and sufficient organ and marrow reserve.²

Enrollment reached 760 patients drawn from 171 participating centers spread across 22 countries, with sites located throughout North America, Europe, South America, and Asia.¹

At the outset, patients were divided equally in a 1:1:1 fashion among 3 arms: TACE combined with STRIDE and lenvatinib (arm A), TACE combined with STRIDE alone (arm B), and TACE without additional systemic therapy (arm C). After 175 patients had been allocated to each arm, the trial shifted to a 1:1 allocation between arms A and C until each reached roughly 275 patients.

All patients received TACE on an as-needed basis alongside their assigned immunotherapy, with or without lenvatinib, then continued on maintenance durvalumab until progression was observed. The trial's primary end point was PFS comparing arm A against arm C, while key secondary end points captured OS between those same arms, plus both PFS and OS when comparing arm B to arm C.^1,2

Key Results

The primary PFS endpoint was met for the durvalumab, tremelimumab, lenvatinib, and TACE arm vs TACE alone, with an OS trend also observed at interim analysis. Arm B similarly showed trends toward improved PFS and OS, though not formally tested. The trial continues to follow OS end points in both investigational arms.

Context and Regulatory Outlook

The STRIDE regimen was previously established as a standard-of-care immunotherapy option in the first-line treatment of unresectable HCC following results from the phase 3 HIMALAYA trial (NCT03298451). In that study, patients with unresectable HCC who received STRIDE demonstrated a meaningful survival advantage over those treated with sorafenib (Nexavar).³ Notably, this survival benefit held up over time, with the regimen continuing to show a favorable and manageable tolerability profile through the 5-year follow-up period.

“EMERALD-3 now shows that bringing the dual immunotherapy STRIDE regimen earlier, alongside TACE and lenvatinib, can further improve outcomes in earlierstage liver cancer,” Susan Galbraith, executive vice president of Oncology Haematology Research and Development at AstraZeneca, concluded in the news release.¹ “This builds on the [HIMALAYA] trial data in patients with advanced, unresectable disease, where the STRIDE regimen has already demonstrated durable [OS] benefit. We are discussing these positive data with global regulatory authorities while awaiting the final results from the key secondary end points.”

REFERENCES

1. Imfinzi plus Imjudo combined with lenvatinib and TACE demonstrated a statistically significant and clinically meaningful improvement in progression-free survival in embolisation-eligible unresectable liver cancer in EMERALD-3 phase III trial. News release. AstraZeneca. April 2, 2026. Accessed April 2, 2026. https://tinyurl.com/3mcvnk93

2. Evaluate durvalumab and tremelimumab +/​- lenvatinib in combination with TACE in patients with locoregional HCC (EMERALD-3). ClinicalTrials.gov. Updated January 15, 2025. Accessed April 2, 2026. https://tinyurl.com/4dy8ecyu

3. Rimassa L, Chan SL, Sangro B, et al. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC. J Hepatol. 2025;83(4):899-908. doi:10.1016/j.jhep.2025.03.033