A prospective, single-center, single-arm clinical study of adjuvant toripalimab combined with axitinib in non-clear renal cell carcinoma (nccRCC) patients with high-risk recurrence factors (IUNU-RC-102).

TPS613 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25–30% of all renal cell carcinoma (RCC) cases and is associated with a poor prognosis. While early-stage treatment typically involves surgery, there is a significant risk of postoperative recurrence. Once recurrence or distant metastasis occurs, management becomes more challenging. Current clinical trial results for metastatic advanced nccRCC have shown variability, and no standard treatment protocol has been established. For advanced clear cell renal cell carcinoma (ccRCC), however, the combination of immunotherapy and targeted therapy has become the standard of care. The RENOTORCH study demonstrated the efficacy and safety of toripalimab combined with axitinib as a first-line treatment for advanced ccRCC[1]. This study aims to investigate the efficacy and safety of toripalimab combined with axitinib as adjuvant therapy in postoperative patients with high-risk nccRCC. Methods: IUNU-RC-102 (NCT05768464) is a single-center, prospective, single-arm clinical trial. The study plans to enroll 30 patients. Key inclusion criteria include: a clinical diagnosis of high-risk recurrent nccRCC following nephrectomy, age between 18 and 75 years, an ECOG performance status of 0–1, no prior systemic therapy for renal cancer, and confirmed pathological histology of nccRCC following partial or radical nephrectomy, with exclusions for clear cell carcinoma, chromophobe carcinoma, and eosinophilic renal cell carcinoma. All participants will receive axitinib (5 mg twice daily) for 4 weeks, along with toripalimab (240 mg intravenously on the first day of each 21-day cycle). The treatment duration will extend up to 52 cycles. The study follows Simon’s minimax two-stage design. In the first stage, three patients will be enrolled and will receive two treatment cycles to assess safety. If dose-limiting toxicity (DLT) occurs in one or more of the three patients, the study will be paused. Investigators will then determine whether to terminate or amend the study protocol after further deliberation. In the second stage, the primary endpoint will be 2-year disease-free survival (DFS). Secondary endpoints will include 3-year overall survival (OS), disease recurrence-specific survival (DRSS), and safety. The first participant was enrolled in IUNU-RC-102 in October 2023. We anticipate that the combination of toripalimab and axitinib will offer a promising new treatment option for these patients. Clinical trial information: NCT05768464 .