Cadonilimab combined with lenvatinib for neoadjuvant therapy in early-stage renal cell carcinoma with indications for partial nephrectomy but high surgical risk: A prospective single-arm phase II clinical trial.

Abstract

530 Background: Partial nephrectomy is the standard treatment for early-stage renal cell carcinoma; however, in some patients, although the tumor is early-stage, the surgical difficulty may preclude its implementation. This study aims to evaluate the efficacy and safety of Cadonilimab combined with Lenvatinib in neoadjuvant therapy for renal cell carcinoma with indications for partial nephrectomy but high surgical risk. Methods: This is a single-center, single-arm Phase II clinical trial. Eligible patients included those with biopsy-confirmed clear cell renal carcinoma who had indications for partial nephrectomy but were at high surgical risk (criteria: 1. tumors measuring 4-7 cm located at the renal hilum or endophytic ≥75%; 2. tumors larger than 7 cm). Patients received Lenvatinib at a dosage of 8 mg or 12 mg QD combined with Cadonilimab at 6 mg/kg every two weeks for 3-6 cycles, for a total treatment duration of 6-12 weeks. Cadonilimab is a first-in-class bispecific antibody targeting both PD-1 and CTLA-4. All patients are scheduled to undergo partial nephrectomy after neoadjuvant therapy. The primary endpoint was the objective response rate (ORR) based on RECIST 1.1 criteria. Secondary endpoints included the renal preservation success rate, safety, and incidence of perioperative complications. Results: A total of 27 patients were enrolled in the study. Sixteen patients completed 6 cycles of Cadonilimab treatment, 6 patients completed 3 cycles, and 5 patients did not complete the pre-set treatment cycles. One patient underwent surgery after experiencing a grade 4 adverse event (diabetic ketoacidosis) following the second cycle of Cadonilimab; four patients discontinued treatment for subjective reasons and proceeded to surgery after the second cycle. All 27 patients underwent surgical procedures. The primary endpoint ORR was 55.6% (15/27), with a tumor control rate of 100%. All patients demonstrated tumor reduction prior to nephrectomy, with an average maximum tumor diameter reduction rate of 26.5%. Furthermore, 100% of patients completed partial nephrectomy. Two patients achieved pathological complete response, and all patients exhibited tumor necrosis, with an average tumor necrosis rate of 45%. Adverse events (AEs) of grade ≥3 occurred in 10.5% of patients, including hyperglycemia and elevated ALT/AST. One patient experienced a grade 4 AE, and no grade 3 postoperative complications were reported. The main limitation of this study is that it is a single-center, small-sample study. Conclusions: Cadonilimab combined with Lenvatinib for neoadjuvant treatment in early clear cell renal carcinoma with indications for partial nephrectomy but high surgical risk demonstrates clear efficacy and safety, warranting further clinical validation. Clinical trial information: NCT06138496 .