4077 Background: Cancer immunotherapy has expanded the treatment options for advanced HCC (aHCC). Atezolizumab plus bevacizumab is approved as the standard of care for patients (pts) with aHCC. QL1706 is a novel dual immune checkpoint blockade containing a mixture of anti-PD-1 IgG4 and anti-CTLA4 IgG1 antibodies (Abs). QL1604 is a humanized mAb against PD-1. The anti-PD-1 Ab of QL1706 has the same protein sequence and was produced by using the same single clone selection method with QL1604. Here we report the safety and efficacy results from a Ph Ib/II study of QL1706 or QL1604 plus bevacizumab (beva) as first-line treatment in pts with aHCC. Methods: Eligible pts had histologically or clinically confirmed HCC; had BCLC stage B/C disease and Child-Pugh class A and B liver function; were systemic therapy naive; and were not suitable for radical surgery and/or locoregional therapy, or progressed after surgery and/or locoregional therapy. This study included 3 parts. Part 1 included a safety run-in phase and an expansion phase. Patients were enrolled to receive QL1706 5 mg/kg plus beva 15 mg/kg Q3W. In part 2, pts were randomized to receive QL1604 200 mg or QL1706 5 mg/kg plus beva 15 mg/kg Q3W. In part 3, pts were enrolled to receive QL1706 7.5 mg/kg plus beva 15 mg/kg Q3W. Initiation of part 3 was to be determined based on factorial analysis on the results from parts 1 and 2. Each treatment cycle lasted for 21 days. Treatment continued until disease progression or other discontinuation events. The primary endpoint was safety. Secondary endpoints included efficacy etc. Results: As of data cutoff (18 Nov 2022), 76 pts were enrolled in parts 1 and 2 (QL1706: 50; QL1604: 26). The baseline characteristics were balanced between the 2 groups. A total of 43 (86%) pts and 23 (88.5%) pts in QL1706 and QL1604 groups experienced TRAEs. For both groups (QL1706 vs QL1604), the most common TRAEs were platelet count decreased (26% vs 23.1%); followed by AST increased (22% vs 19.2%). A total of 17 (34%) pts and 10 (38.5%) pts in QL1706 and QL1604 groups experienced Gr≥3 TRAEs. A total of 25 (50%) pts and 5 (19.2%) pts in QL1706 and QL1604 groups experienced irAEs. The most common irAE in the QL1706 group was rash (16%) (vs 3.8% for QL1604). A total of 8 (16%) pts and 6 (23.1%) pts in QL1706 and QL1604 groups experienced TRSAEs. In the efficacy evaluable population, the ORR was 38.3% (18/47) and 15.4% (4/26) in QL1706 and QL1604 groups. The DCR was 74.5% and 69.2% in QL1706 and QL1604 groups. The mPFS was 6.7 months (95% CI: 3.0-11.4) and 5.4 months (95% CI:2.4-8.5) in QL1706 and QL1604 groups. The mOS was not reached. Conclusions: QL1706 5 mg/kg showed comparable safety profile and numerically higher ORR and longer mPFS vs QL1604 when combined with beva as first-line treatment in pts with aHCC. Ph III head-to-head clinical trial to compare QL1706 or anti-PD-1/PD-L1 Ab plus beva in this population has been planned. Clinical trial information: NCT05603039 .