STRIDE Regimen Shows PFS Benefit Alongside TACE and Lenvatinib in Embolization-Eligible Unresectable HCC

Treatment with single tremelimumab (Imjudo) and regular interval durvalumab (Imfinzi; STRIDE) in combination with lenvatinib (Lenvima) and transarterial chemoembolization (TACE) led to a statistically significant and clinically meaningful prolongation of progression-free survival (PFS) vs TACE alone in patients with unresectable hepatocellular carcinoma (HCC) who are eligible for embolization, meeting the primary end point of the phase 3 EMERALD-3 trial (NCT05301842).¹

In an interim analysis for overall survival (OS), a key secondary end point, a trend toward improved OS was observed with this combination vs TACE alone. Moreover, strong trends toward improved PFS and OS with the STRIDE regimen plus TACE without lenvatinib vs TACE alone were observed, although this was not formally tested at the time of analysis.

The safety profile of each combination evaluated in EMERALD-3 was consistent with the known profiles of each individual medicine, and no new safety findings were identified. Follow-up will continue to further assess OS and other key secondary end points across both investigational arms.

“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. EMERALD‑3 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.

What was the design of EMERALD-3?

EMERALD-3 is a randomized, open-label, sponsor-blinded, multicenter, global phase 3 trial evaluating a single priming dose of tremelimumab (300 mg) added to durvalumab (1500 mg) followed by durvalumab every 4 weeks plus TACE with or without lenvatinib compared with TACE alone.^1,2 Eligible patients were between 18 and 120 years of age and had locoregional HCC that was not amenable to curative therapy but amenable to TACE. Additional eligibility criteria included no evidence of extrahepatic disease, Child Pugh score class A disease, an ECOG performance status of 0 or 1, measurable disease by mRECIST criteria, and adequate organ and marrow function.²

A total of 760 patients were enrolled onto the study across 171 centers in 22 countries, including regions in North America, Europe, South America, and Asia.¹

Patients were first randomly assigned 1:1:1 to receive TACE plus STRIDE and lenvatinib (Arm A), TACE plus STRIDE (Arm B), or TACE alone (Arm C). After each arm reached 175 participants, randomization continued in a 1:1 ratio between Arms A and C until both arms reached approximately 275 patients each.

Patients received the immunotherapy regimen and TACE as needed, with or without concurrent lenvatinib, followed by maintenance durvalumab with or without lenvatinib until disease progression. The study’s primary end point was PFS for Arm A vs Arm C. Key secondary end points included OS for Arm A vs Arm C, as well as PFS and OS for Arm B vs Arm C.^1,2

What’s next for STRIDE in unresectable HCC?

These data will be presented at an upcoming medical meeting and shared with global regulatory authorities to potentially expand the use of the STRIDE regimen in this setting.¹ Currently, patients with embolization-eligible liver cancer often lack systemic treatment options that effectively prevent recurrence or progression.

The STRIDE regimen has already been established as a standard-of-care immunotherapy backbone in first-line unresectable HCC based on data from the phase 3 HIMALAYA trial (NCT03298451), in which the regimen produced an OS benefit over sorafenib (Nexavar) in patients with unresectable HCC.³ This OS benefit was sustained and the regimen maintained a manageable safety profile at 5 years.

“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,” 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://www.astrazeneca.com/media-centre/press-releases/2026/imfinzi-imjudo-improves-pfs-in-early-liver-cancer.html
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://clinicaltrials.gov/study/NCT05301842
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