Treatment with single tremelimumab (Imjudo) and regular interval durvalumab (Imfinzi; STRIDE) in combination with lenvatinib (Lenvima) and transarterial chemoembolization (TACE) statistically significantly improved progression-free survival (PFS) compared with TACE alone in patients with unresectable, embolization-eligible hepatocellular carcinoma (HCC), according to data from the phase 3 EMERALD-3 trial (NCT05301842) presented at the 2026 ASCO Annual Meeting.1
In the intention-to-treat (ITT) population, the median PFS with STRIDE plus lenvatinib plus TACE (Arm A; n = 293) was 13.0 months (95% CI, 12.2-16.7) vs 9.8 months (95% CI, 8.0-11.4) with TACE alone (Arm C; n = 292), representing a 30% reduction in the risk of disease progression or death (HR, 0.70; 95% CI, 0.57-0.86; P = .0007). PFS maturity at the first data cutoff (DCO1; September 2, 2025) was 63.8%.
Having met its primary PFS end point, the study proceeded to evaluate OS for Arm A vs Arm C at DCO2 (February 23, 2026), at which point OS maturity was 40.3%. The median OS was 39.5 months (95% CI, 34.1-not calculable [NC]) for STRIDE plus lenvatinib plus TACE vs 34.7 months (95% CI, 28.8-NC) with TACE alone (HR, 0.84; 95% CI, 0.65-1.09; P = .1814). The study continues to follow patients for final OS.
"TACE is very commonly used worldwide… but sadly only [generates a median PFS of approximately] 8 to 10 months. EMERALD-3 is the first phase 3 clinical trial to demonstrate that a STRIDE-based regimen improved clinical outcomes when combined with TACE, supporting STRIDE as a potential new treatment option for unresectable embolization-eligible HCC.” -Ghassan K. Abou-Alfa, MD, JD, MBA, PhD (hc), FASCO, principal investigator.
Abou-Alfa is an attending physician at Memorial Sloan Kettering Cancer Center, a professor of medicine at Weill Medical School at Cornell University, both in New York, New York, and an adjunct professor at Trinity College Dublin in Ireland.
How was EMERALD-3 designed?
The global, randomized, open-label, sponsor-blinded, multicenter, phase 3 study enrolled patients with pathologically or radiologically confirmed HCC who were not amenable to curative treatment but were eligible for embolization. Patients were required to have Child-Pugh class A liver function and ECOG performance status of 0 or 1, with no extrahepatic disease, no portal vein thrombosis (Vp3 or Vp4), and no prior systemic therapy.
A total of 760 eligible patients were randomly assigned 1:1:1 to 1 of 3 arms:
- Arm A: STRIDE regimen (a single priming dose of tremelimumab at 300 mg added to durvalumab at 1500 mg, followed by durvalumab every 4 weeks) plus lenvatinib plus TACE
- Arm B (n=175): STRIDE plus TACE
- Arm C): TACE alone
Random assignment continued in a 1:1:1 fashion until each arm reached 175 patients, at which point it proceeded 1:1 to Arms A and C until approximately 275 participants were enrolled in each. Stratification factors included geographic region (Japan vs Asia excluding Japan vs rest of the world), prior palliative locoregional therapy, and baseline tumor burden (more vs up to 7 lesions by up to 7 criteria).
The primary end point was PFS assessed by blinded independent central review (BICR) per RECIST 1.1 criteria for Arm A vs Arm C. Key secondary end points included OS for Arm A vs Arm C, and PFS and OS for Arm B vs Arm C. The study employed a hierarchical multiple-testing procedure: Arm A vs C PFS was assessed at DCO1 (September 2, 2025) at an alpha of 0.05, and OS for Arm A vs C was assessed at DCO2 (February 23, 2026) only if the PFS end point was met. Arm B vs C comparisons would then be formally tested only upon meeting the prior end points in sequence.
What Prior Evidence Supported EMERALD-3?
- Use of the STRIDE regimen as a standard-of-care immunotherapy backbone in first-line unresectable HCC was first established in the phase 3 HIMALAYA trial (NCT03298451).
- In HIMALAYA, STRIDE demonstrated durable OS benefit over sorafenib (Nexavar), with sustained benefit through 6 years of follow-up.
- These data provided the mechanistic and clinical rationale for combining STRIDE with locoregional therapy and anti-angiogenic agents in the embolization-eligible setting; positive high-level results from EMERALD-3 were first released in April 2026.
What additional OS data for Arm B were reported at ASCO?
For Arm B vs Arm C—assessed descriptively per the hierarchical testing procedure since the OS end point for Arm A was not formally met—the median PFS with STRIDE plus TACE was 12.9 months (95% CI, 10.2-15.9) compared with 8.1 months (95% CI, 6.5-10.2) for TACE alone (HR, 0.71; 95% CI, 0.56-0.91; nominal P = .0062; PFS maturity 75.1%). The median OS for Arm B vs Arm C also showed a favorable descriptive trend, with a median OS of NC (95% CI, 37.7-NC) for STRIDE plus TACE vs 32.9 months (95% CI, 24.1-43.2) with TACE alone (HR, 0.70; 95% CI, 0.51-0.95; nominal P = .0233; OS maturity 45.4%).
Formal statistical testing for Arm B has not yet been conducted per the pre-specified multiplicity procedure. At the 12-month landmark, PFS rates were 56.2% vs 42.9% for Arm A vs Arm C, and 53.0% vs 38.0% for STRIDE plus TACE vs Arm C. At 24 months, PFS rates were 30.4% vs 19.3% for Arm A vs Arm C, and 30.0% vs 20.3% for Arm B vs Arm C.
A pre-planned exploratory analysis comparing Arm A vs Arm B showed no meaningful difference in PFS across the ITT population or most subgroups (HR, 0.94; 95% CI, 0.73-1.21). Of note, investigators observed that patients without a viral etiology appeared to have a nominally favorable PFS with the addition of lenvatinib (HR, 0.70; 95% CI, 0.44-1.09), whereas viral etiology subgroups did not show the same pattern.
What did the safety analysis show?
The safety profile across all 3 arms was consistent with the known profiles of the individual agents. Grade 3 or 4 adverse effects (AEs) were reported in 71.4% of patients in Arm A (n = 287), 64.0% in Arm B (n = 175), and 28.6% in Arm C (n = 290). Serious AEs occurred in 64.1%, 50.9%, and 23.4% of patients in Arms A, B, and C, respectively.
The incidence of any-grade AEs possibly related to any study treatment was 97.6% in Arm A, 96.0% in Arm B, and 74.1% in Arm C. AEs provoked by TACE were reported in 67.6%, 77.1%, and 74.1% of patients across Arms A, B, and C, respectively.
Treatment interruptions of any investigational product occurred in 84.0% and 44.0% of patients in Arms A and B, respectively. Interruptions of durvalumab specifically affected 59.9% of patients in Arm A and 44.0% of those in Arm B. In arm A, 78.7% and 49.5% of patients required lenvatinib interruptions or dose reductions, respectively. Discontinuation of any investigational product was reported at a rate of 35.5% in Arm A and 20.6% in Arm B. Discontinuation of durvalumab occurred in 23.7% and 20.6% of patients in Arms A and B, respectively; discontinuation of lenvatinib occurred in 30.7% of patients in Arm A.
Subsequent anticancer therapy was received by 43.3% of patients in Arm A and 70.2% in Arm C, and by 50.3% in Arm B vs 75.4% in the corresponding Arm C comparator group.
What is the significance of these data
Vishwanath Sathyanarayanan, MD, MBBS, a medical oncologist and HCC specialist at Apollo Hospitals in Bangalore, India, who provided commentary on the EMERALD-3 data at the press briefing, highlighted the unmet need this trial addresses and offered clinical perspective on the results.
"There is a major unmet need in intermediate HCC; we have a plethora of regimens for advanced HCC, but there is a major unmet need in this subset of patients. I would probably be very cautious in using and selecting the right patient, especially to get the meaningful benefit." -Dr Vishwanath Sathyanarayanan
He further noted that the findings could have particular relevance in regions where TACE is widely used, stating that from a global perspective and in lower- and middle-income countries like India, where TACE is very commonly employed, this study represents a potentially practice-changing development for how intermediate-stage HCC is managed.
References
- Abou-Alfa GK, 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 with unresectable embolization-eligible hepatocellular carcinoma (eeHCC).J Clin Oncol. 2026;44(17 suppl):LBA4000. doi:10.1200/JCO.2026.44.17_suppl.LBA4000
- 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
- AstraZeneca. 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. April 2, 2026. Accessed May 31, 2026. https://www.astrazeneca.com/media-centre/press-releases/2026/imfinzi-imjudo-improves-pfs-in-early-liver-cancer.html
