Tremelimumab (CTLA-4) + durvalumab (PD-L1) ± lenvatinib (VEGFR TKI) with TACE improves PFS in embolization-eligible unresectable HCC (EMERALD-3)

Tremelimumab + durvalumab (STRIDE: single priming dose tremelimumab plus Q4W durvalumab) was combined with transarterial chemoembolization (TACE) with or without lenvatinib (VEGFR/FGFR-targeting multikinase inhibitor) in the Phase 3 EMERALD-3 trial (NCT05301842) in unresectable, embolization-eligible HCC: STRIDE+lenvatinib+TACE (n=293), STRIDE+TACE (n=175), or TACE (n=292). STRIDE+lenvatinib+TACE met the primary endpoint with median PFS 13.0 vs 9.8 months for TACE (HR 0.70, 95% CI 0.57–0.86; p=0.0007); OS was immature (40% events) with a nonsignificant trend (median OS 39.5 vs 34.7 months; HR 0.84; p=0.1814). STRIDE+TACE also improved PFS (median 12.9 vs 8.1 months in the first 175/arm analysis; HR 0.71) and showed an OS benefit signal vs TACE (HR 0.70; OS maturity 45%); grade 3/4 treatment-related AEs were higher with STRIDE+lenvatinib+TACE (62.7%) and STRIDE+TACE (48.6%) vs TACE alone (18.6%), consistent with adding immunotherapy±TKI on top of locoregional therapy.