Efficacy and safety of fruquintinib combined with serplulimab as 1 ^st line treatment in metastatic or unresectable non-clear cell renal cell carcinoma (nccRCC): Updated results from a single-arm, multicentre clinical trial.

542 Background: For advanced non-clear cell renal cell carcinoma (nccRCC), systemic therapy is the main option but the treatment standard remains unclear. In the past decade, promising results have emerged from clinical trials with vascular endothelial growth factor receptor (VEGFR) inhibitors, or anti-programmed death-1 (PD-1) antibodies. Fruquintinib (FRU) is a potent VEGFR inhibitor approved for metastatic colorectal cancer. This trial aims to evaluate the efficacy and safety of FRU combined with serplulimab (an anti-PD-1 antibody) in patients (pts) with advanced nccRCC. Methods: This is a multicentre single-arm prospective trial planning to enroll 39 pts with pathologically confirmed metastatic or unresectable nccRCC. Eligible patients were 18 to 80 years old with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1, and had not received prior systemic therapy. All pts received FRU (5mg, qd, po, 2w on/1w off) plus serplulimab (4.5mg/kg, d1, i.v.gtt, q3w). The primary endpoint was progression-free survival (PFS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), safety, etc. Results: As of Sep.20 th , 2024, 16 nccRCC pts were enrolled. The median age was 63.5 years (range 24-78) and 75.0% were male. Seven (43.8%) pts had an ECOG PS of 2. Histologically, papillary subtype was the most prevalent (12, 75.0%), followed by chromophobe (2, 12.5%), 1 collecting duct carcinoma and 1 unclassified subtype, and sarcomatoid features were observed in 5 (31.3%) patients. The metastatic sites were primarily lymph nodes (56.3%), lungs (37.5%), peritoneum (25.0%) and abdominal cavity (25.0%). Among the 16 evaluable pts, 8 achieved partial response and 6 had stable disease, resulting in an ORR of 50.0% (95% CI: 25.5%-74.5%) and a DCR of 87.5% (95% CI: 61.7%-98.4%). Three pts experienced rapid progression, all with sarcomatoid features (2 papillary, 1 chromophobe). The median PFS was not reached. The most common treatment-related adverse events (TRAEs) were rash (37.5%), fever (31.3%), ALT increased (25.0%), AST increased (25.0%), hypertension (18.8%), hypothyroidism (18.8%), fatigue (18.8%) and most were grade 1/2 except 1 pt experiencing grade 3 AST increased. Conclusions: The preliminary data showed promising efficacy and tolerable toxicity of FRU combined with serplulimab in pts with metastatic or unresectable nccRCC. Clinical trial information: NCT05831891 .