Camrelizumab (C) plus rivoceranib (R) with transarterial chemoembolization (TACE) vs TACE alone in unresectable hepatocellular carcinoma (uHCC): A randomized, phase 3 trial.

4001 Background: The combination of C (anti–PD-1 antibody) + R (VEGFR2 tyrosine kinase inhibitor) significantly improved progression-free survival (PFS) and overall survival (OS) vs sorafenib as first-line treatment for advanced HCC, and improved event-free survival vs surgery alone as perioperative treatment for resectable HCC. We conducted a phase 3 trial evaluating C+R with TACE in intermediate-stage HCC and here present data from the protocol-specified PFS interim analysis (IA). Methods: In this multicenter, open-label, phase 3 trial, patients (pts) with TACE-eligible uHCC, Child-Pugh A, ECOG performance status (PS) 0–1 and no extrahepatic spread were randomized 1:1 to receive C (200 mg, iv, Q3W) + R (250 mg, po, QD) + TACE or TACE alone. TACE (cTACE or DEB-TACE) was administered at the investigator (INV)’s discretion; C+R continued until loss of clinical benefits, unacceptable toxicities, or other protocol-specified criteria. The primary endpoint was PFS by BIRC per mRECIST. As of Sep.13, 2025, 214 PFS events occurred and a preplanned IA was performed. Results: 423 pts (ECOG PS 1, 22.9%; AFP ≥400 ng/mL, 26.7%; portal vein invasion vp1/2, 9.7%) were randomized to C+R+TACE (n=214) or TACE (n=209). As of data cutoff, median follow-up was 16.4 mo. Median PFS by BICR per mRECIST was significantly longer with C+R+TACE vs. TACE (11.1 vs. 8.3 mo; HR 0.73 95% CI 0.56–0.96; 1-sided p=0.0127). PFS by BICR per RECIST v1.1 (13.9 vs 9.5 mo; HR 0.67 95% CI 0.50–0.91) and by INV per mRECIST (13.8 vs 7.0 mo; HR 0.61 95% CI 0.47–0.81) and per REIST v1.1 (15.7 vs 8.4 mo; HR 0.61 95% CI 0.45–0.81) showed consistent findings (Table 1). PFS benefits with addition of C+R persisted across most prespecified subgroups. OS was not mature, with an early trend favoring C+R+TACE (HR 0.76 95% CI 0.46–1.24); OS was 91.4% vs 85.5% at 12 mo, and 82.0% vs 73.3% at 24 mo. Among treated pts, grade ≥3 TRAEs occurred in 73.7% (157/213) in C+R+TACE arm vs. 28.7% (60/209) in TACE arm; of them, the most common in C+R+TACE arm were increased AST (20.7% vs 12.9%), hypertension (19.7% vs 4.3%), increased ALT (17.8% vs 9.6%), and decreased platelet count (11.3% vs 2.9%). Conclusions: C+R+TACE provided statistically significant and clinically meaningful improvement in PFS vs TACE, with manageable safety, supporting this regimen as a potential new treatment option for TACE-eligible uHCC. Follow-up for OS is ongoing. Clinical trial information: NCT05320692 . PFS outcomes (ITT set). BIRC INV C+R+TACE (n=214) TACE (n=209) C+R+TACE (n=214) TACE (n=209) Per mRECIST Median (95% CI), mo 11.1 (7.8–14.0) 8.3 (6.9–9.5) 13.8 (8.5–17.3) 7.0 (5.7–9.5) HR (95% CI)* 0.73 (0.56–0.96); 1-sided p=0.0127 † 0.61 (0.47–0.81) Per RECIST v1.1 Median (95% CI), mo 13.9 (10.9–19.4) 9.5 (8.1–11.1) 15.7 (10.3–19.6) 8.4 (6.9–10.8) HR (95% CI)* 0.67 (0.50–0.91) 0.61 (0.45–0.81) *Stratified Cox proportional hazard model. †Stratified Log-Rank test.