Sequential transarterial chemoembolization and stereotactic body radiotherapy followed by immunotherapy using single tremelimumab regular interval durvalumab in locally advanced, unresectable HCC (START-FIT using STRIDE): A single-arm, phase II, multi-centre study.

540 Background: START-FIT (sequential transarterial chemoembolization, stereotactic body radiotherapy, plus anti-PD-L1 and anti-CTLA-4 immunotherapy) shows promise in locally advanced HCC. We evaluated its activity using anti-PD-L1 and anti-CTLA-4. Methods: Patients aged ≥18 with unresectable HCC (≥5cm, ≤3 nodules, Child-Pugh A-B7) were enrolled. Exclusions included extrahepatic metastasis and main portal vein (VP4) or IVC (VV3) invasion. Patients underwent TACE, 5-fraction SBRT (27.5-40 Gy), then Tremelimumab (300 mg) and Durvalumab (1500 mg) starting 7 days post-SBRT, every 4 weeks. Primary endpoint: ORR by mRECIST 1.1; secondary endpoints: PFS, OS, LC, TRAEs. Results: From 2020 to 2024, 33 patients (44 tumors) were enrolled; median age 67 (50–82), 91% male. Median tumor size was 11.1 cm (5.6–24.7), with 73% (24/33) showing macrovascular invasion (hepatic vein n=14, portal vein n=5, both n=5). Median follow-up was 21 months (5.6–53). The ORR was 72.7% (24/33; 95% CI 57.5–87.9%), with 42.4% (14/33) achieving CR and 30.3% (10/33) PR. Stable disease was seen in 9.1% (3/33), PD in 12.1% (4/33). Two patients were not evaluable. Among CR patients, 42.4% (14/33) were under surveillance; 21.2% (7/33) converted to curative treatments (resection n=3, ablation n=4). The 18-month LC was 96.6% (95% CI 90.1–100%), PFS 61.8% (44.1–79.4%), OS 90% (79.4–100%). Grade ≥3 TRAEs occurred in 36.3% (12/33), mainly transient AST/ALT elevations (n=5). Four patients (12.1%) had grade ≥3 immune-related adverse events. Conclusions: START-FIT using STRIDE is safe and effective in locally advanced unresectable HCC resulted in 42% CR rate with an additional of 21% patients converted to curative surgery. Clinical trial information: NCT 04988945 . Patient and tumor characteristics. N=33 Age, median (range), years 67 (50-82) SexMaleFemale 30 (90.9%)3 (9.1%) ECOG performance status01 29 (87.9%)4 (12.1%) Aetiology of liver cirrhosisHepatitis BMultiple etiologiesCryptogenic 26 (78.8%)3 (9.1%)4 (12.1%) Child-Pugh scoreA5A6 28 (84.8%)5 (15.2%) Albumin Bilirubin Score (ALBI)Grade 1Grade 2 19 (57.6%)14 (42.4%) BCLC stageA-BC without extra-hepatic spread 9 (27.3%)24 (72.7%) Reasons of Unresectable Inadequate liver remnant volume, poor ICG, or unable to achieve R0 resection, or bothBCLC stage B beyond up-to-sevenBCLC stage C without extra-hepatic spread 8 (24.2%)1 (3.1%)24 (72.7%) Tumor vascular invasionNoYesBranched portal vein invasionHepatic vein invasionBoth portal vein and hepatic vein invasion 9 (27.3%)24 (72.7%)5 (15.2%)14 (42.3%)5 (15.2%) Number of lesion(s)12-3 22 (66.7%)11 (33.3%) Size of largest lesion, median (range), cm 5.6 (11.1-21.8) Sum of largest diameters of lesions, median (range), cm 11.1 (5.6-24.7) Baseline AFP, nmol/L≤ 400 ng/ml> 400 ng/ml 23 (69.7%)10 (30.3%)