Academic Depth Report
Editor’s Note: During the recent ASCO GU 2025 (Genitourinary Cancers Symposium), Professor Jiwei Huang from Renji Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine (on behalf of the research team led by Ding Yingjie), presented the updated efficacy and safety data from a multicenter, single-arm, Phase II trial. The study evaluates the combination of Fruquintinib and Serplulimab as a first-line (1st-line) treatment for patients with metastatic or unresectable non-clear cell renal cell carcinoma (nccRCC).
01 Background: Therapeutic Challenges in Advanced nccRCC
Non-clear cell renal cell carcinoma (nccRCC) accounts for approximately 20%–25% of all renal cell carcinomas. Due to its heterogeneous histological subtypes, nccRCC often demonstrates limited sensitivity to traditional cytokines and certain targeted therapies. While VEGF inhibitors combined with immune checkpoint inhibitors (ICIs) have become the standard of care for clear cell RCC, robust clinical evidence for 1st-line treatment in the nccRCC population remains scarce. This study explores the potential of combining Fruquintinib, a highly selective VEGFR 1/2/3 inhibitor, with Serplulimab, a novel PD-1 inhibitor.
02 Study Design and Patient Baseline
This multicenter, single-arm, Phase II trial enrolled 39 treatment-naive patients with metastatic or unresectable nccRCC. • Treatment Regimen: Fruquintinib (oral, 2 weeks on / 1 week off) combined with Serplulimab (intravenous infusion, every 3 weeks [Q3W]). • Endpoints: The primary outcome was Progression-Free Survival (PFS). • Baseline Characteristics: The median age of the cohort was 43.5 years. Histologically, 48.7% of patients had papillary renal cell carcinoma (pRCC), and 30.2% of cases exhibited sarcomatoid features.
03 Efficacy Results: Deep Response and Sustained Survival
Among 36 evaluable patients with a median follow-up of 10 months, the combination therapy demonstrated significant anti-tumor activity: • Response Rates: The Objective Response Rate (ORR) reached 52.8%, and the Disease Control Rate (DCR) was 97.2%. Waterfall plots indicated that the majority of patients experienced significant target lesion shrinkage. • Survival Data: The median PFS has not yet been reached. The 9-month PFS rate was 87.3%. • Subgroup Observation: Notably, three patients experienced rapid disease progression, all of whom presented with sarcomatoid features, suggesting a distinct biological aggressiveness and potential resistance mechanisms in this specific subgroup.
04 Safety Profile: Manageable Toxicities
Safety analysis indicated that the combination of Fruquintinib and Serplulimab was generally well-tolerated. Common treatment-related adverse events (TRAEs) included: • Rash, proteinuria, and hypertension. • No Grade 4 or 5 TRAEs were reported. All adverse events were manageable through standard clinical interventions.
05 Biomarker and Subgroup Analysis
The presentation highlighted the significance of biomarkers in refining therapeutic strategies. Initial analyses suggested a positive association between PD-L1 expression levels and ORR. Given that papillary RCC accounted for nearly half of the cohort, the research team plans to conduct further stratified analyses specifically for this subtype to better understand its clinical benefit.
06 Conclusion and Future Outlook
The combination of Fruquintinib and Serplulimab as a 1st-line treatment for advanced nccRCC demonstrates promising anti-tumor activity with an acceptable and manageable safety profile. Although the study is limited by its single-arm design and relatively short follow-up duration, these findings provide crucial clinical evidence for the management of nccRCC and support further investigation of this TKI plus ICI regimen in larger, randomized controlled trials.
