Anlotinib combined with sintilimab as first-line treatment in patients with advanced non-clear cell renal cell carcinoma (nccRR): Preliminary results from an exploratory prospective multicentre clinical study.

4526 Background: Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 25% of all kidney cancers, however, the effect of systemic chemotherapy is limited. We report the first results of a single-arm, phase 2 study (NCT05220267) evaluating the efficacy and safety of anlotinib (a multi-target tyrosine kinase inhibitor) combined with sintilimab (a monoclonal antibody against programmed cell death protein 1) as first-line treatment in patients with advanced nccRCC. Methods: Patients with histologically confirmed advanced nccRCC and measurable disease per RECIST v1.1 who had not previously received systemic therapy were received anlotinib (12 mg qd, d1-14, repeated every 21 days) plus sintilimab (200 mg IV Q3W) till disease progression or intolerant toxicity. The primary endpoint is progression-free survival (PFS); secondary endpoints include objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: From April 2022 to January 2024, 44 patients were enrolled with a median age of 46 years (range: 18-79), 13 (29.5%) had Fumarate deficient RCC, 10 (22.7%) had Papillary RCC, 9 (20.5%) had TFE3 rearranged RCC and 12 (27.3%) were unclassified. Among these participants, 44 patients were evaluable. 95.5% were IMDC intermediate- or poor-risk, 72.7% had prior nephrectomy and 97.7% had synchronous metastatic disease. ORR and DCR were 56.8%（95%CI 41.6-72.1）and 86.4%（95%CI 75.8-96.9）, respectively.≥1 and ＜1 Combined Positive Score of PD-L1 expression were observed in 50% (22/44) and 38.6% (17/44) patients respectively, and the ORR was 72.7% (95%CI:52.2-92.9) and 41.2% (95%CI: 15.1-67.3) in the two groups. As of November 13, 2024, median follow-up time was 17.5m (95%CI 14.9-20.1). The median PFS was 13.6m (95%CI 8.6-18.6). Treatment-related grade 3/4 adverse events were observed in 22.7% (10/44) of the patients, encompassed proteinuria (3 patients, 7%), hyponatremia (2 patients, 4%), hypertension (1 patients, 2%), hepatic insufficiency (1 patients, 2%), fatigue(1 patients, 2%), rash (1 patients, 2%), decreased lymphocyte count (1 patients, 2%). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: Our results showed promising efficacy and acceptable toxicity of anlotinib plus sintilimab for patients with advanced nccRCC. Clinical trial information: NCT05220267 .