Cadonilimab (anti-PD-1 and CTLA-4 bispecific antibody) combined with axitinib for the first-line treatment of advanced or metastatic non-clear renal cell carcinoma: A prospective, single-arm, phase Ib/II study.

544 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of all renal cell carcinoma (RCC) and lacks standards of care. More recent data suggests the efficacy of anti-PD-(L)1 plus anti-CTLA-4 and immune checkpoint inhibitors combined with tyrosine-kinase inhibitors in the RCC. Cadonilimab (AK104) is a first-in-class tetravalent bispecific antibody that targets both PD-1 and CTLA-4, showing a manageable safety profile and favorable clinical benefits. Here we explore the efficacy and safety of cadonilimab in combination with axitinib in patients with advanced or metastatic nccRCC. Methods: Eligible patients had histologically confirmed advanced or metastatic nccRCC who had not previously received systemic therapy. Patients received cadonilimab (10 or 15 mg/kg q3w in phase Ib, and 10mg/kg q3w in phase II) in combination with axitinib (5mg bid) as first-line treatment until disease progression or intolerant to treatment. The primary endpoints were safety and objective response rate (ORR; RECIST v1.1). This study is registered with ClinicalTrials.gov, NCT05808608. Results: As of October 1, 2024, 26 patients were enrolled, median follow-up was 5.1 months (0.6-10.7 months). Twenty patients were available for efficacy assessment. Confirmed ORR was 55% (11/20), and disease control rate (DCR) was 95% (19/20). The median progression-free survival (PFS) was not reached. All patients experienced treatment-related adverse events (TRAEs), grade≥3 TRAEs occurred in 12 (46.2%) patients. Conclusions: Cadonilimab combined with axitinib demonstrated promising antitumoral efficacy and manageable toxicities in patients with advanced or metastatic nccRCC. The trial is an ongoing study, and complete results are awaited after completion of the enrollment and longer follow-up. Clinical trial information: NCT05808608 .