947P - The efficacy and safety of cadonilimab combined with lenvatinib for first-line treatment of advanced hepatocellular carcinoma: A phase Ib/II clinical trial

Background

Immunotherapy, targeted therapy and their combination has been developed as first-line treatment for advanced HCC.The combination therapy has improved the antitumor effects compared with targeted therapy,but tended to have higher incidence of adverse reactions.This study aims to assess the efficacy and safety of Cadonilimab, a humanized, tetravalent, bispecific antibody targeting PD-1 and CTLA-4,with lenvatinib(len) in first-line treatment of HCC.

Methods

This multicenter, open-label, phase Ib/II study included patients with histologically or clinically confirmed unresectable HCC to receive either 6mg/kg Cadonilimab every 2 weeks plus len(cohort A) or 15mg/kg Cadonilimab every 3 weeks plus len(cohort B). The primary endpoint was objective response rate (ORR) by RECIST v1.1, the secondary endpoint includes safety, progression-free disease (PFS), overall survival (OS), disease control rate (DCR), duration of response (DoR) and time to response (TTR).

Results

A total of 59 patients were enrolled (cohort A, n=31; cohort B, n=28).As the date of data cutoff July 28,2023, the median follow-up duration was 27.4 months.ORR was 35.5% (95% CI, 23.6-49.1) in cohort A and 35.7% (95% CI, 18.6-55.9) in cohort B. The median PFS was 8.6 months (95%CI, 5.2-17.9) and 9.8 months (6.9-15.2), respectively.The median OS was 27.1 months （95%CI，15.7,NE) for cohort A,while it was not reached for cohort B. Grade ≥ 3 TRAEs occured in 66.1% of patients, and serious AEs were reported in 39.0% of cases.All AEs were expected and manageable.All the deaths were related to disease progression and not related to Cadonilimab. Table: 947P

Summary of Efficacy analysis and tumor response by investigator review per RECIST v1.1

Conclusions

This novel combination therapy of PD-1/CTLA4 bispecific monoclonal antibody and lenvatinib showed promising efficacy and manageable toxicity that could provide an option of treatment in first-line setting of aHCC.

Clinical trial identification

NCT04444167.

Editorial acknowledgement

Legal entity responsible for the study

Akeso Biopharma, Inc.

Funding

Akeso Biopharma, Inc.

Disclosure

All authors have declared no conflicts of interest.