Adjuvant toripalimab in high-risk renal cell carcinoma after tumor resection (TUOAD-RCC): A prospective phase 2 study.

e16520 Background: Adjuvant pembrolizumab therapy after surgery for renal-cell carcinoma (RCC) improved overall survival (OS) and disease-free survival (DFS), However, the other immune checkpoint inhibitors (ICIs), including atezolizumab and nivolumab±ipilimumab, failed to have effect on disease control. The contradictory results represent effective adjuvant therapy for patients with high-risk RCC following surgery still unmet need. This study is to assess the efficacy and safety of adjuvant toripalimab in high-risk RCC following nephrectomy. Methods: This was an open-label phase 2 clinical trial including patients with resectable high-risk RCC who received nephrectomy or partial nephrectomy followed by adjuvant toripalimab (at a dose of 240mg) every 21 days for 17 cycles. Participants were enrolled from October 2022 to December 2024. DFS, OS and safety (adverse events [AEs] and patient-reported quality-of-life) were both primary end points. The secondary end points were immune biomarkers. RNA and DNA were isolated from pretreatment tumor tissue was subjected to RNA and next-generation sequencings. Results: Forty-four patients were enrolled between July 2022 and September 2024, 38 of them received adjuvant toripalimab after nephrectomy or partial nephrectomy and were included in intention-to-treat (ITT) analysis. The median time from surgery to data-cutoff date (January 17, 2025) was 10.3 months (range from 1.2 to 28.7). There was only one progressed disease in the 38 patients occurred at 25.0 months after the beginning of adjuvant toripalimab. The percentage of patients who remained alive and disease-free at 24 months were both 100% after a moderate follow-up time. AEs of any grade emerged in 30 patients after receiving toripalimab, the most common ones were rash (n = 10, 26.3%), hypoadrenocorticism (n = 8, 21.1%), hyperthyroidism (n = 7, 18.4%) and fatigue (n = 7, 18.4%). Grade 3 or higher adverse events of any cause occurred in 2 patients (5.3%), including myocardial and hepatic injuries, result in treatment discontinuation. Additional 12 patients refused to continue adjuvant toripalimab because of low grade AEs or other reasons. The 14 patients who discontinued toripalimab received a median of 7 cycles (range from 1 to 16) treatment. All patients completed the Functional Assessment of Cancer Therapy Kidney Symptom Index–Disease-Related Symptoms (FKSI-DRS) assessments and The Cancer Quality of Life Questionnaire (EORTC QLQ-C30) questionnaires. The least-squares mean change from baseline to week 52 in the FKSI-DRS score was −1.75 (95%CI, −0.47 to −3.02). Each score of function and symptom from EORTC QLQ-C30 didn’t show significant change. Conclusions: Our data preliminarily demonstrated the safety and efficacy of adjuvant toripalimab in RCC at high-risk of recurrence or progression. Clinical trial information: NCT06584435 .