Background
Global, randomised, open-label, sponsor-blinded phase 3 (177 sites, 21 countries). N=760 (full analysis set). Unresectable HCC amenable to TACE, Child-Pugh A, ECOG 0–1, ≥1 measurable intrahepatic lesion (mRECIST). STRIDE = single tremelimumab + regular-interval durvalumab. Randomised 1:1:1 (STRIDE+lenvatinib+TACE / STRIDE+TACE / TACE) until STRIDE+TACE reached 175, then 1:1 to ~275 per arm. Stratified by region, tumour burden, prior palliative embolisation.
Results
Interventions and follow up: Arm A: Tremelimumab 300 mg ×1 + durvalumab 1500 mg q4w (up to 36 cycles) + lenvatinib 8/12 mg daily + TACE (first TACE ≥7 days after first durvalumab)
Arm B: STRIDE + TACE (no lenvatinib)
Arm C: TACE alone (within 7 days of randomisation)
Primary endpoint: PFS, Arm A vs C
mFollow up: 10.0 mo (PFS, 1st cutoff Sept 2025); 24.6 vs 22.9 mo (OS, 2nd cutoff Feb 2026)
Results: PFS (A vs C, primary): 13.0 vs 9.8 mo; HR 0.70 (95% CI 0.57–0.86); P=.0007
OS (A vs C, interim): 39.5 vs 34.7 mo; HR 0.84 (95% CI 0.65–1.09); P=.18
PFS (B vs first 175 TACE): 12.9 vs 8.1 mo; HR 0.71 (95% CI 0.56–0.91)
OS (B vs C): NR
ORR: NR in abstract
Arm B: STRIDE + TACE (no lenvatinib)
Arm C: TACE alone (within 7 days of randomisation)
Primary endpoint: PFS, Arm A vs C
mFollow up: 10.0 mo (PFS, 1st cutoff Sept 2025); 24.6 vs 22.9 mo (OS, 2nd cutoff Feb 2026)
Results: PFS (A vs C, primary): 13.0 vs 9.8 mo; HR 0.70 (95% CI 0.57–0.86); P=.0007
OS (A vs C, interim): 39.5 vs 34.7 mo; HR 0.84 (95% CI 0.65–1.09); P=.18
PFS (B vs first 175 TACE): 12.9 vs 8.1 mo; HR 0.71 (95% CI 0.56–0.91)
OS (B vs C): NR
ORR: NR in abstract
Adverse events
Most common grade 3–4: hypertension 12% (Arm A); post-embolisation syndrome 6% and anaemia 6% (Arm B); post-embolisation syndrome 6% (Arm C)
Serious AEs: 64% vs 51% vs 23%
Treatment-related deaths: 7 (2%; incl. 2 myocarditis, hepatic failure, HLH) vs 0 vs 2 (1%)
Serious AEs: 64% vs 51% vs 23%
Treatment-related deaths: 7 (2%; incl. 2 myocarditis, hepatic failure, HLH) vs 0 vs 2 (1%)
Conclusions
STRIDE plus lenvatinib plus TACE significantly improved PFS versus TACE alone (13.0 vs 9.8 mo, HR 0.70) in embolisation-eligible unresectable HCC; STRIDE plus TACE without lenvatinib showed a similar PFS effect (HR 0.71). Interim OS not significant. Supports adding systemic immunotherapy to TACE in intermediate-stage HCC, with lenvatinib's incremental contribution unclear.
Key Limitations
Open-label (sponsor-blinded only). Short PFS follow-up (median 10 mo) with immature OS (HR 0.84, P=.18). Adaptive enrolment: Arm B compared only with the first 175 TACE patients, and A vs B was not formally powered, so lenvatinib's added value cannot be judged. Surrogate primary endpoint (PFS) in a setting where TACE is repeatable and OS is long. Triplet carried 64% serious AEs and 2% treatment-related deaths; TACE technique/number at investigator discretion. Doublet PFS gain similar to triplet raises question of whether lenvatinib adds only toxicity.
Clinical Context
EMERALD-1 (durvalumab + bevacizumab + TACE) and LEAP-012 (lenvatinib + pembrolizumab + TACE) previously showed PFS but not OS benefit; ESMO/AASLD/NCCN still list TACE (or TARE) as standard for BCLC-B, with systemic therapy reserved for TACE-unsuitable or progressing disease. EMERALD-3 is the third positive PFS trial of IO + TACE; none has yet shown OS benefit or FDA approval in this setting. STRIDE monotherapy (HIMALAYA) is FDA/EMA approved for unresectable HCC. Presented ASCO 2026 (LBA4000).