News|Articles|July 8, 2026

STRIDE Plus TACE With or Without Lenvatinib Improves Responses in Embolization-Eligible HCC

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Key Takeaways

mRECIST and RECIST 1.1 analyses consistently favored STRIDE+lenvatinib+TACE over TACE alone for PFS, ORR, DCR, and DOR, supporting additive activity beyond locoregional therapy.
EMERALD-3 enrolled patients with Child-Pugh A liver function, ECOG performance status of 0 or 1, and no extrahepatic disease or Vp3/Vp4 invasion; they were randomly assigned to STRIDE+lenvatinib+TACE, STRIDE+TACE, or TACE alone with RECIST 1.1 BICR PFS primary.
Arm A achieved median PFS ~13 months and reduced progression/death risk (HR, ~0.67-0.70) vs TACE; ORR gains were more pronounced by mRECIST than RECIST 1.1.
Arm B (STRIDE+TACE) showed descriptive improvements in PFS and an OS HR of 0.70 vs TACE, but comparisons were not powered for formal significance per hierarchy.
Treatment intensification increased grade 3/4 and serious AEs and led to frequent interruptions/discontinuations, with hypertension, post-embolization syndrome, and endocrine/toxicities aligning with known STRIDE, lenvatinib, and TACE profiles.

Tumor response assessments by both RECIST 1.1 and modified RECIST (mRECIST) criteria showed improved progression-free survival (PFS), objective response rate (ORR), and duration of response (DOR) with the STRIDE regimen—single tremelimumab (Imjudo), regular-interval durvalumab (Imfinzi)—with or without lenvatinib (Lenvima) plus transarterial chemoembolization (TACE) vs TACE alone in patients with embolization-eligible hepatocellular carcinoma (HCC), according to analyses from the phase 3 EMERALD-3 trial (NCT05301842) presented at the 2026 European Society for Medical Oncology Gastrointestinal Cancers Congress.¹

Per mRECIST criteria, the median PFS by blinded independent central review (BICR) was 12.9 months with STRIDE plus lenvatinib plus TACE (arm A; n = 293) vs 8.3 months for TACE alone (arm C; n = 292; HR, 0.67); these values were 10.4 months (95% CI, 10.0-12.9) vs 6.7 months (95% CI, 6.4-8.3) per investigator assessment (HR, 0.64; 95% CI, 0.53-0.77).

At the first data cutoff (DCO1) of September 2, 2025, the confirmed ORRs for arm A vs arm C were 36.6% vs 30.0% per RECIST 1.1 criteria by BICR (OR, 1.37; 95% CI, 0.96-1.95) and 58.9% vs 42.5% per mRECIST criteria by investigator (OR, 1.99; 95% CI, 1.42-2.79). By mRECIST criteria per BICR, the ORRs were 67.8% vs 54.8%, respectively. The disease control rates (DCR) at 20 weeks per RECIST 1.1 criteria were 78.8% vs 65.5% in arms A vs C, respectively, and the median DOR favored arm A per both RECIST 1.1 criteria (15.7 months [95% CI, 9.5-not calculable (NC)] vs 13.3 months [95% CI, 7.2-NC]) and mRECIST by investigator (13.1 months [95% CI, 7.4-29.4] vs 10.2 months [95% CI, 4.9-15.7]).

Why do the EMERALD-3 tumor response data matter?

TACE has been a global standard of care for patients with embolization-eligible HCC for more than 20 years, but the median PFS with TACE alone is approximately 8 to 10 months. EMERALD-3 is the first phase 3 study to demonstrate that a STRIDE-based regimen, combined with TACE, improves clinical outcomes in embolization-eligible disease.^1,2

Primary PFS results from this study were first reported at the 2026 American Society of Clinical Oncology Annual Meeting.² In the intention-to-treat (ITT) population, the median PFS in arm A was 13.0 months (95% CI, 12.2-16.7) vs 9.8 months (95% CI, 8.0-11.4) in arm C, representing a 30% reduction in the risk of disease progression or death (HR, 0.70; 95% CI, 0.57-0.86; P = .0007). The PFS data maturity at DC01 was 63.8%.

At the second data cutoff of February 23, 2026, at which point the overall survival (OS) data maturity was 40.3%, the median OS was 39.5 months (95% CI, 34.1-NC) in arm A vs 34.7 months (95% CI, 28.8-NC) in arm C (HR, 0.84; 95% CI, 0.65-1.09; P = .1814).

How was the EMERALD-3 trial designed?

EMERALD-3 was a global, randomized, open-label, sponsor-blinded, multicenter study that enrolled 760 patients with pathologically or radiologically confirmed HCC not amenable to curative treatment but amenable to embolization.^1,2Patients needed to have Child-Pugh A disease, an ECOG performance status of 0 or 1, no extrahepatic disease, no Vp3 or Vp4 portal vein invasion, and no prior systemic therapy. Patients were randomly assigned 1:1:1 to arm A, arm B (STRIDE plus TACE; n = 175), or arm C until each arm reached 175 patients, after which randomization continued 1:1 to arms A and C. Stratification factors were geographic region, prior palliative locoregional therapy, and baseline tumor burden by the Up-to-7 criteria.

STRIDE consisted of tremelimumab at 300 mg on day 1 plus durvalumab at 1500 mg on day 1 and then every 4 weeks; lenvatinib was dosed daily; and TACE (drug-eluting bead or conventional) began at least 7 days after immunotherapy in arms A and B or within 7 days of randomization in arm C. Treatment continued for up to 36 months. The primary end point was PFS for arm A vs arm C per RECIST 1.1 criteria by BICR. Key secondary end points included OS for arms A vs C, PFS for arms B vs C, and OS for arms B vs C; other secondary end points included ORR, DCR, DOR, time to progression, time to second progression, patient-reported outcomes, and safety.

What did descriptive tumor response analyses in arm B show?

Comparisons involving arm B were descriptive per the prespecified testing hierarchy.¹ The median PFS values for arm B vs arm C per RECIST 1.1 criteria by BICR were 12.9 months (95% CI, 10.2-15.9) vs 8.1 months (95% CI, 6.5-10.2), respectively (HR, 0.71; 95% CI, 0.56-0.91; nominal P = .0062); these respective values were 12.0 months (95% CI, 9.9-14.1) vs 6.6 months (95% CI, 6.3-8.0) per mRECIST criteria by investigator (HR, 0.59; 95% CI, 0.46-0.75). The descriptive OS comparison for arm B vs arm C yielded an HR of 0.70 (95% CI, 0.51-0.95; nominal P = .0233).

What did the safety analysis of EMERALD-3 show?

Any-grade adverse effects (AEs) occurred in 99.7% of patients in arm A, 98.9% of those in arm B, and 88.3% of those in arm C. Grade 3 or 4 AEs possibly related to study treatment were reported in 62.7%, 48.6%, and 18.6% of patients, respectively, and serious AEs occurred in 64.1%, 50.9%, and 23.4% of patients, respectively. AEs led to interruption of any study investigational product in 84.0% of patients in arm A and 44.0% of those in arm B, and to discontinuation of any study investigational product in 35.5% and 20.6% of patients, respectively.

The most common any-grade AEs in arm A included postembolization syndrome (29.3%), hypothyroidism (37.6%), hypertension (35.2%), diarrhea (33.4%), and decreased appetite (33.4%). The most common maximum grade 3 or 4 AEs in arm A were hypertension (11.8%) and postembolization syndrome (8.4%). The investigators concluded that the safety profile was acceptable and consistent with the known profiles of STRIDE, lenvatinib, and TACE.

References

Erinjeri JP, Ren Z, Abou-Alfa GK, et al. Tumour response analyses by RECIST v1.1 and mRECIST in the phase III EMERALD-3 study of tremelimumab plus durvalumab with or without lenvatinib plus transarterial chemoembolisation (TACE) in embolisation-eligible hepatocellular carcinoma (eeHCC). Ann Oncol. 2026;37(suppl 1):S71. doi:10.1016/j.annonc.2026.06.007
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(suppl 17):LBA4000. doi:10.1200/JCO.2026.44.17_suppl.LBA4000