Preliminary data of a phase Ib/II trial evaluating the efficacy and safety of adebrelimab, camrelizumab plus apatinib as first-line therapy in patients with advanced hepatocellular carcinoma.

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e16221 Background: The CARES-310 study has demonstrated that the combination of the anti-PD-1 antibody camrelizumab and the VEGFR2 tyrosine kinase inhibitor apatinib exhibits improved progression-free survival (PFS) and overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). We conducted this study to investigate whether the addition of the anti-PD-L1 antibody adebrelimab to camrelizumab and apatinib would further improve clinical outcomes. Methods: This is a prospective, phase 1b/2 clinical trial employing the i3 + 3 dose escalation design. Eligibility includes adults with unresectable or metastatic HCC, a ECOG PS of 0 or 1, a Child-Pugh score ≤ 7, and at least one measurable lesion per RECIST v 1.1. In phase 1b, patients (pts) received adebrelimab (10 mg/kg or 20 mg/kg, I.V., D1, Q3W), camrelizumab (200mg, I.V., D1, Q3W), and apatinib (250 mg orally daily). Phase 2 is a single arm, open-label trial in the first-line setting. The primary objective were dose-limiting toxicity (DLT), maximal tolerated dose (MTD), and recommended phase II dose (RP2D). With α = 0.05 and 80% power, the pts needed for stage I and total of the Simon 2-stage design was 17 and 41 pts, respectively. Results: As of 4 February 2024, 6 HCC pts progressed after or were intolerant to first-line treatment (systemic therapy ± surgical resection) were treated in 1 dose cohorts. 1 DLT occurred (Grade 3 elevated blood bilirubin increased). The RP2D was adebrelimab (10 mg/kg), camrelizumab (200mg), and apatinib (250 mg). The most common drug-related AEs were Hypertension (83.3%) and Rash (50%); and Serum amylase increased, Itching, ALT/AST increased, and Hypothyroidism (each 33.3%). Immune-related AEs were similar to those seen with other checkpoint blockade agents. No drug-related AEs led to death. 1 pts (16.7%) discontinued due to drug-related AEs. Conclusions: The combination of Adebelimumab, Camrelizumab, and Apatinib demonstrated manageable safety for unresectable HCC. Enrollment in the phase II trial is ongoing and updated clinical data will be presented. Clinical trial information: NCT05924997 .