QL1706 (PD-1/CTLA-4 bispecific antibody) plus bevacizumab specific for patients with hepatocellular carcinoma combined with lung metastasis: A secondary analysis of a prospective, single-arm, phase Ib/II study.

4114 Background: Hepatocellular carcinoma (HCC) with lung metastasis carries a dismal prognosis, and effective systemic treatments remain limited. Bispecific antibodies targeting multiple immune checkpoints have emerged as promising therapeutic strategies. This study assessed the efficacy and safety of QL1706, a PD-1/CTLA-4 bispecific antibody, in combination with bevacizumab in patients with HCC and lung metastases. Methods: This was a secondary analysis of a multicenter, phase Ib/II clinical trial. Eligible patients with unresectable, advanced HCC and confirmed lung metastases received QL1706 (5.0 or 7.5 mg/kg, cohort A) or QL1604 (PD-1 antibody, 200 mg, cohort B) plus bevacizumab every three weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) per RECIST v1.1. Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: In cohort A, 15 patients were included in this analysis. At a median follow-up of 19.2 months, the ORR was 53.3% (95% CI, 26.6–78.7) and the DCR was 73.3% (95% CI, 44.9–92.2). Median PFS was 9.9 months (IQR, 1.6–NE), with a 1-year PFS rate of 46.7%, and the 2-year OS was 66.7%. Among the 7 patients with measurable lung target lesions, the ORR was 71.4% (95% CI, 29.0–96.3), including 2 complete responses. In cohort B, 5 patients were included, with a median follow-up of 23.7 months. The ORR was 20.0% (95% CI, 0.5–71.6) and the DCR was 60.0% (95% CI, 14.7–94.7). Treatment-related adverse events occurred in 93.3% of patients in cohort A and 100.0% in cohort B, with grade ≥3 TRAEs observed in 53.3% and 40.0% of patients, respectively. Most adverse events were manageable, and no treatment-related deaths were reported. Conclusions: QL1706 plus bevacizumab demonstrated promising antitumor activity and a manageable safety profile in patients with HCC and lung metastases. The high response rate observed in lung lesions highlights the potential of intensified immunotherapy combined with anti-VEGF therapy for this subgroup, warranting further validation in phase III trials. Clinical trial information: NCT05603039 . Treatment-emergent adverse events of QL1706 / QL1604 and bevacizumab. All grades Grade ≥ 3 Cohort A (N = 15) Cohort B (N = 5) Cohort A (N = 15) Cohort B (N = 5) TEAEs 15 (100.0) 5 (100.0) 10 (66.7) 4 (80.0) irAEs 11 (73.3) 0 2 (13.3) 0 TRAEs 14 (93.3) 5 (100.0) 8 (53.3) 2 (40.0) Associated with QL1706 / QL1604 14 (93.3) 5 (100.0) 6 (40.0) 2 (40.0) Associated with bevacizumab 14 (93.3) 5 (100.0) 8 (53.3) 3 (60.0)