Anlotinib plus everolimus as first-line treatment for advanced non–clear cell renal cell carcinoma: A single-center, single-arm, phase II trial.

e16533 Background: For patients (pts) with recurrent or stage IV non-clear cell renal cancer (nccRCC),the medical treatment guidelines recommend the first choice to participate in clinical trials, or use TKI drugs such as sunitinib, and mTOR inhibitors such as everolimus. Anlotinib is a novel multi-target tyrosine kinase inhibitor (TKI). It’s antitumor targets include vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-kit. ALTER-UC-001 is a single-center, single-arm, phase II trial which evaluated the efficacy and tolerability of anlotinib plus everolimus as first-line therapy in pts with nccRCC (NCT05124431). Methods: Patients with advanced nccRCC and no prior systemic drug therapy for advanced disease were eligible for this trial; Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The patients received 12mg anlotinib once daily on days 1-14 every 3 weeks by oral, and 5mg everolimus orally once daily. The primary endpoint was objective response rate (ORR). Secondary endpoints included overall disease control rate (DCR), progression free survival (PFS), and over survival (OS). Adverse events will be monitored throughout the study and graded according to CTCAE V5.0. Results: Between Jan 2022 and Dec 2023, 24 pts were enrolled and received study treatment. The median age was 56 years old (range: 20 to 79 years). Nineteen pts (79.2%; 19/24) had a ECOG PS score of 1, and five pts (20.8%; 5/24) had a ECOG PS score of 0. All pts had not received prior treatment. In addition, 17 (70.8%) had received surgical treatment and 1 (4.2%) had received radiotherapy. The data cutoff was Dec 2023, with a median follow-up of 6.04 (range, 1.34-18.1) months.14 pts had the best overall response (unconfirmed) assessments which inferred the ORR of 57.1%(PR in 8 pts 95% CI, 29.6-81.2)and the DCR of 100% (PR in 8 pts and SD in 6 pts; 95% CI, 73.2-100). The median PFS has not reached. Any grades of adverse events (AEs) were observed in 91.7% (22/24) of pts, the most common of which were mucositis (29.1%), hypertension (25.0%) , creatinine increased(16.7%), proteinuria (16.7%) and glutamic-pyruvic transaminase increased (12.5%).Seven (29.1%) pts experienced grade 3 TRAEs, including hypertension (8.3%), proteinuria (8.3%), mucositis (4.2%), platelet count decreased (4.2%), creatinine increased (4.2%), chronic gastritis (4.2%) and bleeding (4.2%). No treatment-related deaths occurred. Three (12.5%) and two (8.3%) pts had suspension of treatment because of TRAEs caused by everolimus and anlotinib respectively. Conclusions: Anlotinib plus everolimus as first-line therapy is efficacious and safe for pts with advanced nccRCC. We will report more data in the future. Clinical trial information: NCT05124431 .