274MO - Efficacy and safety of fruquintinib combined with serplulimab as 1st line treatment in advanced non-clear cell renal cell carcinoma (nccRCC): A single-arm, multicentre clinical trial

Background

For advanced nccRCC, systemic therapy is the main option but the treatment standard remains unclear. In past decade, promising results were seen in 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 is aimed to explore the efficacy and safety of FRU combined with serplulimab (an anti-PD-1 antibody) in advanced nccRCC.

Methods

This is a multicentre single-arm prospective trial planning to enrol 39 patients (pts) with pathologically confirmed metastatic or unresectable nccRCC. Pts should be 18∼80 years old with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and have received no 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 first 6 pts were enrolled as safety run-in to evaluate the safety. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), adverse events (AEs), etc.

Results

As of Apr.1st, 2024, 10 pts were enrolled. The median age was 62.5 years (range 24-73) and 60% were male. Histologically, papillary subtype was the most prevalent (70%), followed by chromophobe (20%) and other types (10%). The metastatic sites were primarily lymph nodes (50%) and lungs (30%). For the 9 evaluable pts, 3 achieved partial response and 3 had stable disease, with an ORR of 33.3% (95% CI: 7.5%, 70.1%) and a DCR of 66.7% (95% CI: 29.9%, 92.5%). Rapid progression occurred in 2 pts with papillary and 1 pt with chromophobe, who were found to have sarcomatoid features. Median PFS was not reached. No dose-limiting toxicity was observed. The most common treatment-related AEs (TRAEs) were rash (50%), fever (50%), ALT increased (40%), AST increased (40%), hypertension (30%), hypothyroidism (30%) and most were grade 1/2 except 1 pt experiencing grade 3 AST increased.

Conclusions

The preliminary data showed encouraging efficacy and tolerable toxicity of FRU combined with serplulimab in pts with advanced nccRCC.

Clinical trial identification

NCT05831891.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.