EMERALD-3 Durvalumab Combo Improves PFS in Embolization-Eligible HCC

The combination of durvalumab (Imfinzi), tremelimumab (Imjudo), and lenvatinib (Lenvima) plus transarterial chemoembolization (TACE) significantly improved progression-free survival (PFS) for patients with unresectable hepatocellular carcinoma (HCC) eligible for embolization, according to a press release from the developer, AstraZeneca.¹ Findings from the phase 3 EMERALD-3 trial (NCT05301842) indicated that adding dual immunotherapy and a multikinase inhibitor to locoregional therapy provides a statistically significant and clinically meaningful benefit compared with TACE alone in this setting.

“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,” said Ghassan Abou-Alfa, MD, JD, MBA, PhD(hc), attending physician and professor of Medicine at Memorial Sloan Kettering Cancer Center, and principal investigator of the EMERALD-3 trial, in the press release.¹ “EMERALD‑3 shows we can now significantly reduce the risk of disease progression with STRIDE as the immunotherapy backbone alongside lenvatinib and TACE.”

What are the primary efficacy and safety findings for the EMERALD-3 trial?

The primary end point of PFS was met by the combination arm evaluating durvalumab and tremelimumab administered via the STRIDE regimen—single tremelimumab regular interval durvalumab—plus lenvatinib and TACE. At an interim analysis, this combination also demonstrated a trend toward improvement in overall survival (OS), a key secondary end point.

Safety results from EMERALD-3 were consistent with the established profiles of durvalumab, tremelimumab, and lenvatinib individually, with no new safety signals identified during the trial.¹

These results will be presented at an upcoming medical meeting and discussed with global regulatory authorities.

How was the EMERALD-3 trial designed for patients with HCC?

The phase 3 EMERALD-3 trial was a randomized, open-label, multicenter study that enrolled 760 patients across 171 centers in 22 countries. Patients with histologically or cytologically confirmed unresectable HCC who were eligible for embolization and had not received prior systemic therapy were randomly assigned 1:1:1 to receive either the durvalumab/tremelimumab/lenvatinib plus TACE combination, the STRIDE regimen plus TACE, or TACE alone.² Patients in the investigational arms received the STRIDE regimen, which consisted of a single 300-mg dose of tremelimumab and 1500 mg of durvalumab every 4 weeks, with or without lenvatinib.

Eligibility criteria required patients to have an ECOG performance status of 0 or 1 and Child-Pugh Class A liver function.² Exclusion criteria included disease amenable to curative surgery, ablation, or transplantation, as well as history of hepatic encephalopathy.

The primary end point of the study was PFS for the quadruplet regimen vs TACE alone. Secondary end points included OS for the quadruplet regimen, as well as PFS and OS for durvalumab plus tremelimumab and TACE vs TACE alone.

Susan Galbraith, executive vice president of Oncology Hematology Research & Development at AstraZeneca, said, “EMERALD‑3 now shows that bringing the dual immunotherapy STRIDE regimen earlier, alongside TACE and lenvatinib, can further improve outcomes in earlier‑stage liver cancer. This builds on the HIMALAYA phase 3 trial [NCT03298451] 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.”¹

The referenced data from the phase 3 HIMALAYA trial ultimately led to the approval of durvalumab and tremelimumab for patients with unresectable HCC in October 2022.³

References

1. Imfinzi plus Imjudo combined with lenvatinib and TACE demonstrated a statistically significant and clinically meaningful improvement in progression-free survival in embolization-eligible unresectable liver cancer in EMERALD-3 phase III trial. News release. AstraZeneca. April 2, 2026. Accessed April 2, 2026. https://tinyurl.com/yesrt38e
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/yc49vtz
3. Imjudo (tremelimumab) in combination with Imfinzi approved in the US for patients with unresectable liver cancer. News Release. AstraZeneca. October 24, 2022. Accessed April 2, 2026. https://tinyurl.com/nzrzhry6