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

Tumor response assessments by both RECIST 1.1 and modified RECIST (mRECIST) 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 ESMO Gastrointestinal Cancers Congress.¹

Per mRECIST criteria, the median PFS by blinded independent central review (BICR) was 12.9 months for Arm A vs 8.3 months for Arm C (HR, 0.67) and 10.4 months (95% CI, 10.0-12.9) vs 6.7 months (95% CI, 6.4-8.3) by investigator assessment (HR, 0.64; 95% CI, 0.53-0.77).

At the first data cutoff (DCO1) of September 2, 2025, confirmed ORR for Arm A vs Arm C was 36.6% vs 30.0% per RECIST 1.1 criteria by BICR (odds ratio [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, ORR was 67.8% vs 54.8%.¹ DCR at 20 weeks was 78.8% vs 65.5% per RECIST 1.1, and median DoR favored Arm A both per RECIST 1.1 criteria (15.7 vs 13.3 months) and per mRECIST by investigator (13.1 vs 10.2 months).

Why do the EMERALD-3 tumor response data matter?

TACE has been a global standard of care for embolization-eligible HCC for more than 20 years, but median PFS with TACE alone is approximately 8 to 10 months, and most patients progress within 1 year. EMERALD-3 is the first phase 3 study to show 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 ASCO Annual Meeting.² 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 DC01 was 63.8%.

At the second data cutoff of 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]) 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, phase 3 study that enrolled 760 patients with pathologically or radiologically confirmed HCC not amenable to curative treatment but amenable to embolization, Child-Pugh A liver function, ECOG performance status of 0 or 1, no extrahepatic disease, no Vp3 or Vp4 portal vein invasion, and no prior systemic therapy.¹ Patients were randomly assigned 1:1:1 to Arm A (STRIDE plus lenvatinib plus TACE; n = 293), Arm B (STRIDE plus TACE; n = 175), or Arm C (TACE; n = 292) 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 300 mg on day 1 plus durvalumab 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, for up to 36 months.¹ 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 Arm A vs C, PFS for Arm B vs C, and OS for Arm B vs C, tested hierarchically; other secondary end points included PFS by mRECIST criteria, objective response rate (ORR), disease control rate (DCR), DOR, time to progression, PFS2, 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. The median PFS for STRIDE plus TACE (Arm B) vs TACE was 12.9 months vs 8.1 months per RECIST v1.1 by BICR (HR, 0.71; 95% CI, 0.56-0.91; nominal P = .0062) and 12.0 months vs 6.6 months per mRECIST by investigator (HR, 0.59; 95% CI, 0.46-0.75).¹ For OS, Arm A vs Arm C did not reach statistical significance at this interim analysis (median, 39.5 vs 34.7 months; HR, 0.84; 95% CI, 0.65-1.09; stratified log-rank P = .1814; boundary, .021) at 40.3% maturity; the descriptive OS comparison for Arm B vs Arm C yielded an HR of 0.70 (95% CI, 0.51-0.95). The study continues to follow participants for final OS.

What did the safety analysis show?

Any-grade adverse effects (AEs) occurred in 99.7% of patients in Arm A, 98.9% in Arm B, and 88.3% in Arm C.¹ 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%. AEs led to interruption of any study investigational product in 84.0% of Arm A and 44.0% of Arm B, and to discontinuation of any study investigational product in 35.5% and 20.6%, respectively.

The most common any-grade AEs in Arm A included post-embolization syndrome (39.4%), 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 post-embolization syndrome (8.4%). Investigators concluded that the safety profile was acceptable and consistent with the known profiles of STRIDE, lenvatinib, and TACE, and that EMERALD-3 is the first phase 3 study to show that a STRIDE-based regimen combined with TACE improves clinical outcomes in embolization-eligible HCC.

Disclosures: Erinjeri reported receiving consulting and advisory fees from AstraZeneca.

References

1. Erinjeri JP, Ren Z, Abou-Alfa GK, et al. Tumour response analyses by RECIST v1.1 and mRECIST in the phase 3 EMERALD-3 study of tremelimumab plus durvalumab with or without lenvatinib plus transarterial chemoembolisation in embolisation-eligible hepatocellular carcinoma. Presented at: 2026 ESMO Gastrointestinal Cancers Congress; July 1-4, 2026; Munich, Germany. Abstract LBA2.
2. 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