Durvalumab/Tremelimumab STRIDE-Based Regimens Boost PFS in HCC

Combining the STRIDE regimen of durvalumab (Imfinzi) plus tremelimumab (Imjudo) with transarterial chemoembolization (TACE) with or without lenvatinib (Lenvima) significantly improved progression-free survival (PFS) over TACE alone in patients with unresectable embolization-eligible hepatocellular carcinoma (eeHCC), with a favorable overall survival (OS) trend also observed, according to findings from the phase 3 EMERALD-3 trial (NCT05301842) shared at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.^1,2,3

The primary end point of the EMERALD-3 trial—PFS for STRIDE plus lenvatinib plus TACE vs TACE alone—was met with statistical significance at the first data cutoff of September 2, 2025. Among 585 intention-to-treat (ITT) patients, the STRIDE-lenvatinib-TACE arm (n = 293) achieved a median PFS of 13.0 months (95% CI, 12.2-16.7) vs 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 vs the prespecified significance boundary of P = .0315).¹ PFS maturity was 63.8%, with a median follow-up of 11.0 months for the STRIDE-lenvatinib-TACE arm and 8.3 months for the TACE arm.^1,2 PFS rates at 12, 18, and 24 months were 56.2%, 42.1%, and 30.4% for STRIDE-lenvatinib-TACE vs 42.9%, 30.8%, and 19.3% for TACE alone, respectively.^1,2

At the second data cutoff of February 23, 2026, the interim OS analysis for STRIDE-lenvatinib-TACE vs TACE did not reach statistical significance. Median OS was 39.5 months (95% CI, 34.1-not calculable) for STRIDE-lenvatinib-TACE vs 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 vs the significance boundary of P = .021).¹ OS maturity was 40.3%, with a median follow-up of 24.6 months for STRIDE-lenvatinib-TACE and 22.9 months for TACE alone.^1,2 The 12-, 18-, and 24-month OS rates were 83.2%, 77.5%, and 66.9% in the STRIDE-lenvatinib-TACE arm vs 82.0%, 69.7%, and 61.5% in the TACE-alone arm, respectively.^1,2,3 A total of 112 deaths (38.2%) occurred in the STRIDE-lenvatinib-TACE arm vs 124 deaths (42.5%) in the TACE-alone arm. The study continues to follow patients for the final OS analysis.¹

The STRIDE-plus-TACE arm (arm B; n = 175) also demonstrated clinically meaningful improvements vs TACE alone (first 175 patients). Median PFS was 12.9 months (95% CI, 10.2-15.9) vs 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 alone. The 12-, 18-, and 24-month PFS rates were 53.0%, 38.8%, and 30.0% for STRIDE plus TACE vs 38.0%, 29.8%, and 20.3% for TACE alone, respectively.^1,2

For OS, the STRIDE-plus-TACE arm showed a median OS that was not calculable (95% CI, 37.7-not calculable) 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%). The 12-, 18-, and 24-month OS rates were 87.7%, 76.4%, and 68.0% for STRIDE plus TACE vs 81.5%, 67.3%, and 57.8% for TACE alone, respectively.^1,2

A preplanned exploratory comparison of STRIDE plus lenvatinib plus TACE vs 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, alpha-fetoprotein level, Barcelona Clinic Liver Cancer stage, ECOG performance status, and virology status. This suggests that lenvatinib did not meaningfully augment the efficacy of STRIDE in combination with TACE and points to STRIDE itself as the primary driver of benefit in the ITT population.^1,2

“In the embolization-eligible setting for hepatocellular carcinoma, [TACE] has been the most practiced global standard of care for over 2 decades. However, outcomes remain poor, with a median [PFS] 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, a gastrointestinal medical oncologist at Memorial Sloan Kettering Cancer Center in New York, New York.³

EMERALD-3 Safety Data

The safety profile of STRIDE plus lenvatinib plus TACE was consistent with the known profiles of the individual agents, although 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-lenvatinib-TACE arm, in 98.9% in the STRIDE-plus-TACE arm, and in 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.^1,2,3

Serious AEs were reported in 64.1% of patients in the STRIDE-lenvatinib-TACE arm, in 50.9% in the STRIDE-plus-TACE arm, and in 23.4% in the TACE-alone arm. AEs leading to discontinuation of any investigational agent occurred in 35.5% of patients in the STRIDE-lenvatinib-TACE arm and in 20.6% of patients receiving STRIDE plus TACE; discontinuation of durvalumab specifically occurred in 23.7% and 20.6%, respectively. In the STRIDE-lenvatinib-TACE arm, interruption of lenvatinib occurred in 78.7% of patients and dose reductions occurred in 49.5%. AEs provoking TACE-related reactions were comparable across all 3 arms, with grade 3/4 TACE-provoked AEs occurring in 25.1%, 22.3%, and 18.6% of the STRIDE-lenvatinib-TACE, STRIDE-plus-TACE, and TACE-alone arms, respectively.^1,2

EMERALD-3 Study Design and Patient Population

EMERALD-3 is a global, randomized, open-label, sponsor-blinded, multicenter phase 3 clinical trial enrolling 760 patients across 3 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.¹

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 vs Asia excluding Japan vs rest of world), prior palliative locoregional therapy, and baseline tumor burden (within or beyond up-to-7 criteria). The primary end point was PFS for arm A vs arm C by blinded independent central review per RECIST v1.1; key secondary end points included OS for arm A vs arm C, and PFS and OS for arm B vs arm C.¹

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 vs sorafenib (Nexavar) through 6 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.^1,2

Expert Insight on EMERALD-3 Results

In a news release issue by ASCO, Vishwanath Sathyanarayanan, MD, DM, Lead Oncosciences, Karnataka Region, at Apollo Hospitals in Bangalore, India, offered his expert interpretation on the real-world relevance of the EMERALD-3 data and their potential to change global medical practice.³

“The significant improvement in [PFS] observed in the phase 3 EMERALD-3 study positions this combinatorial regimen of [STRIDE plus TACE], with or without lenvatinib, as a compelling therapeutic option for patients with unresectable embolization-eligible hepatocellular carcinoma,” Sathyanarayanan said.³ “These findings are likely to influence clinical practice and may be considered practice changing for medical oncologists treating hepatocellular carcinoma globally.”

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 (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC). J Clin Oncol. 2026;44(suppl 17). Abstract 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. Accepted manuscript.

3. EMERALD-3 study shows that new combination treatment strategies for embolization-eligible hepatocellular carcinoma are superior. News release. American Society of Clinical Oncology. June 1, 2026. Accessed June 1, 2026. https://www.asco.org/about-asco/press-center/new-combination-treatment-strategies-embolization-eligible-liver-cancer