LBA36 Final analysis of RATIONALE-301: Randomized, phase III study of tislelizumab versus sorafenib as first-line treatment for unresectable hepatocellular carcinoma

Tislelizumab (TIS), an anti-PD-1 monoclonal antibody, has demonstrated durable responses and was well tolerated as monotherapy in 2L+ treatment patients (pts) previously treated systemically for unresectable HCC (Ducreux et al, 2021). TIS been further evaluated against sorafenib (SOR) a global randomized Phase 3 study (RATIONALE-301; NCT03412773) 1L adult pts with HCC. Systemic therapy-naïve adults histologically confirmed BCLC Stage B/C who were not amenable to or progressed after loco-regional therapy, Child-Pugh A, ≥1 measurable lesion per RECIST v1.1, ECOG PS ≤1 eligible. Pts 1:1 receive (200 mg IV Q3W) SOR (400 PO BID) until disease progression, intolerable toxicity, withdrawal, no longer benefiting from therapy. The primary endpoint OS; secondary endpoints included ORR, PFS, DOR by blinded independent review committee, safety. Non-inferiority of OS between tested the non-inferiority margin 1.08. A total 674 (n=342, TIS; n=332, SOR); at data cutoff (11 Jul 2022) minimum follow up 33 months (mo). In this final analysis, RATIONALE-301 met its (mOS: 15.9 mo [TIS] vs 14.1 [SOR]; stratified HR: 0.85 [95.003% CI: 0.712, 1.019]). associated higher ORR (14.3% 5.4%) more (mDoR: 36.1 11.0 mo) compared SOR. Median PFS 2.2 3.6 (HR: 1.1 [95% 0.92, 1.33]). duration (4.1 2.7 mo). safety profiles both treatments consistent prior reports. Incidence rates grade ≥3 AEs (48.2% 65.4%) leading discontinuation (10.9% 18.5%) lower SOR; death low across (4.4%, 5.2%, SOR). Immune-mediated occurring ≥5% TIS-treated hepatitis (5.3%) hypothyroidism (5.3%). Single-agent clinically meaningful benefit that non-inferior favorable profile option