EMERALD-3 Trial Shows Improved PFS in Unresectable Liver Cancer

Patients with with unresectable embolization-eligible hepatocellular carcinoma (eeHCC) experienced significant improvements in progression-free survival (PFS) with the STRIDE regimen of durvalumab (Imfinzi) plus tremelimumab (Imjudo) and transarterial chemoembolization (TACE) with or without lenvatinib (Lenvima) vs TACE alone, according to a presentation on data from the phase 3 EMERALD-3 trial (NCT05301842) at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.^1-3

The primary end point of EMERALD-3, PFS for STRIDE plus lenvatinib plus TACE (Arm A) versus TACE alone (Arm C), was met with statistical significance at the first data cutoff of September 2, 2025. Among 585 intention-to-treat (ITT) patients, the STRIDE plus lenvatinib plus TACE arm (n = 293) achieved a median PFS of 13.0 months (95% CI, 12.2-16.7) versus 9.8 months (95% CI, 8.0-11.4) in the TACE-alone arm (n = 292), representing a 30% reduction in the risk of progression or death (HR, 0.70; 95% CI, 0.57-0.86; P = .0007, versus the pre-specified significance boundary of P = .0315).1 PFS maturity was 63.8%, with a median follow-up of 11.0 months for the STRIDE plus lenvatinib plus TACE arm and 8.3 months for the TACE arm. PFS rates at 12, 18, and 24 months were 56.2%, 42.1%, and 30.4% for STRIDE plus lenvatinib plus TACE versus 42.9%, 30.8%, and 19.3% for TACE alone, respectively.

At the second data cutoff of February 23, 2026, the interim OS analysis for STRIDE plus lenvatinib plus TACE versus TACE did not reach statistical significance. Median OS was 39.5 months (95% CI, 34.1-not calculable) versus 34.7 months (95% CI, 28.8-not calculable) with TACE alone, corresponding to an HR of 0.84 (95% CI, 0.65-1.09; P = .1814, versus the significance boundary of P = .021).¹ OS maturity was 40.3%, with a median follow-up of 24.6 months for STRIDE plus lenvatinib plus TACE and 22.9 months for TACE. The 12-, 18-, and 24-month OS rates were 83.2%, 77.5%, and 66.9% in the STRIDE plus lenvatinib plus TACE arm versus 82.0%, 69.7%, and 61.5% in the TACE arm, respectively. A total of 112 deaths (38.2%) occurred in the STRIDE plus lenvatinib plus TACE arm versus 124 deaths (42.5%) in the TACE arm. The study continues to follow patients for the final OS analysis.

The STRIDE plus TACE arm (Arm B; n = 175), also demonstrated clinically meaningful improvements versus TACE alone (first 175 patients). Median PFS was 12.9 months (95% CI, 10.2-15.9) versus 8.1 months (95% CI, 6.5-10.2; HR, 0.71; 95% CI, 0.56-0.91; nominal P = .0062), with PFS maturity of 75.1% and a median follow-up of 10.3 months for STRIDE plus TACE and 7.7 months for TACE.1 The 12-, 18-, and 24-month PFS rates were 53.0%, 38.8%, and 30.0% for STRIDE plus TACE versus 38.0%, 29.8%, and 20.3% for TACE alone, respectively.

For OS, the STRIDE plus TACE arm showed a median OS that was not calculable (95% CI, 37.7-not calculable) versus 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%).1 The 12-, 18-, and 24-month OS rates were 87.7%, 76.4%, and 68.0% for STRIDE plus TACE versus 81.5%, 67.3%, and 57.8% for TACE alone, respectively.

A pre-planned exploratory comparison of STRIDE plus lenvatinib plus TACE versus STRIDE plus TACE across key subgroups showed an overall HR of 0.94 (95% CI, 0.73-1.21), with generally consistent results across subgroups including geographic region, baseline tumor burden, AFP level, BCLC stage, ECOG performance status, and virology status, suggesting that lenvatinib did not meaningfully augment the efficacy of STRIDE in combination with TACE, and pointing to STRIDE itself as the primary driver of benefit in the ITT population.

“In the embolization-eligible setting for hepatocellular carcinoma, transarterial chemoembolization has been the most practiced global standard of care for over 2 decades. However, outcomes remain poor, with a median progression-free survival of 8 to 10 months. Repeated TACE procedures wane in effect over time and risk further decline in liver function. Currently there are no systemic therapy-based options approved for these patients globally,” said lead study author Ghassan K. Abou-Alfa, MD, PhD, MBA, JD, FASCO.³

EMERALD-3 Safety Data

The safety profile of STRIDE plus lenvatinib plus TACE was consistent with the known profiles of the individual agents, though higher rates of adverse events (AEs) were observed compared with TACE alone. Any-grade AEs were reported in 99.7% of patients in the STRIDE plus lenvatinib plus TACE arm, 98.9% in the STRIDE plus TACE arm, and 88.3% in the TACE-alone arm. Grade 3 or 4 AEs occurred in 71.4%, 64.0%, and 28.6% of patients, respectively, with those possibly related to any study treatment occurring in 62.7%, 48.6%, and 18.6%, respectively.

Serious AEs were reported in 64.1% of STRIDE plus lenvatinib plus TACE patients, 50.9% of STRIDE plus TACE patients, and 23.4% of TACE-alone patients. AEs leading to discontinuation of any investigational product occurred in 35.5% of STRIDE plus lenvatinib plus TACE patients and 20.6% of STRIDE plus TACE patients; discontinuation of durvalumab specifically occurred in 23.7% and 20.6%, respectively. In the STRIDE plus lenvatinib plus TACE arm, interruption of lenvatinib occurred in 78.7% of patients and dose reduction in 49.5%. AEs provoking TACE-related reactions were comparable across all three arms, with grade 3/4 TACE-provoked AEs occurring in 25.1%, 22.3%, and 18.6% in the respective arms.

EMERALD-3 Study Design and Patient Population

EMERALD-3 (NCT05301842) is a global, randomized, open-label, sponsor-blinded, multicenter phase 3 study enrolling 760 patients across three arms: STRIDE plus lenvatinib plus TACE (Arm A; n = 293), STRIDE plus TACE (Arm B; n = 175), and TACE alone (Arm C; n = 292). Randomization was initially 1:1:1 until each arm reached 175 patients, after which it continued 1:1 between Arms A and C.

Eligible patients had pathologically or radiologically confirmed HCC that was not amenable to curative treatment but amenable to embolization, Child-Pugh class A, ECOG performance status 0 or 1, no extrahepatic disease, no portal vein thrombosis of Vp3 or Vp4 grade, and no prior systemic therapy. Stratification factors included geographic region (Japan versus Asia excluding Japan versus rest of world), prior palliative locoregional therapy, and baseline tumor burden (within or beyond Up-to-7 criteria). The primary endpoint was PFS for Arm A versus Arm C by blinded independent central review per RECIST v1.1; key secondary endpoints included OS for Arm A versus C, and PFS and OS for Arm B versus C.

TACE has been a global standard of care for unresectable eeHCC for more than 20 years, with historical median PFS of 8 to 10 months. STRIDE is an established frontline standard of care in advanced HCC based on demonstrated OS benefit over sorafenib through six years of follow-up. The EMERALD-3 results represent the first phase 3 demonstration that a STRIDE-based regimen can improve clinical outcomes when combined with TACE, potentially establishing a new treatment option for patients with unresectable eeHCC.

Expert Insight on EMERALD-3 Results

“The significant improvement in progression-free survival observed in the phase 3 EMERALD-3 study positions this combinatorial regimen of single tremelimumab regular interval durvalumab (STRIDE) plus transarterial chemoembolization (TACE), with or without lenvatinib, as a compelling therapeutic option for patients with unresectable embolization-eligible hepatocellular carcinoma. These findings are likely to influence clinical practice and may be considered practice-changing for medical oncologists treating hepatocellular carcinoma globally,” said ASCO Expert Vishwanath Sathyanarayanan, MD, DM, Lead Oncosciences, Karnataka Region, Apollo Hospitals, Bangalore, India.3

References

1. 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. J Clin Oncol. 2026;44(suppl 16). J Clin Oncol 44, 2026 (suppl 17; abstr LBA4000). doi:10.1200/JCO.2026.44.17_suppl.LBA4000
2. Kudo M, Abou-Alfa GK, Ren Z, et al. Durvalumab and tremelimumab, with or without lenvatinib, combined with transarterial chemoembolisation in participants with embolisation-eligible hepatocellular carcinoma (EMERALD-3): a global, randomised, open-label, sponsor-blinded, phase 3 study. Lancet Oncol. 2026; accepted for publication (in press).
3. American Society of Clinical Oncology. New combination treatment strategies for embolization-eligible liver cancer. ASCO press release. May 29, 2026. Accessed June 1, 2026. https://ac.asco.org/about-asco/press-center/new-combination-treatment-strategies-embolization-eligible-liver-cancer