At the 2025 Annual Meeting of the American Society of Clinical Oncology (ASCO), Professor Jiwei Huang, on behalf of the research team, delivered an oral presentation reporting the latest efficacy and safety data from a multicenter, single-arm, Phase II clinical study. The trial evaluated fruquintinib in combination with serplulimab as a first-line treatment for patients with metastatic or unresectable non–clear cell renal cell carcinoma (nccRCC).01 Background: High Unmet Need for Effective First-Line nccRCC Therapy
Non-clear cell renal cell carcinoma (nccRCC) is characterized by significant histological heterogeneity, and the standard of care for first-line treatment remains an area of active exploration. While the combination of vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) and programmed cell death protein 1 (PD-1) inhibitors has become a cornerstone in advanced renal cell carcinoma management, the optimal combination for the nccRCC subtype has yet to be fully established. This study evaluates the clinical utility of fruquintinib, a highly selective VEGFR 1/2/3 inhibitor, in combination with the anti-PD-1 antibody serplulimab in this specific population.
02 Study Design: The “2+1” Targeted-Immune Combination Regimen
The study enrolled 39 treatment-naïve patients with metastatic or unresectable nccRCC. The therapeutic regimen consisted of oral fruquintinib (administered on a “2-weeks-on/1-week-off” schedule) combined with intravenous serplulimab (administered every 3 weeks). The primary endpoint of the study was progression-free survival (PFS).
Among the 38 evaluable patients at baseline, the median age was 53 years. Histological analysis revealed that 50% of patients had papillary RCC, and 30% exhibited sarcomatoid features. The most common metastatic sites were the lymph nodes and lungs.
03 Efficacy Results: 9-Month PFS Rate Reaches 87.3% with Superior Disease Control
With a median follow-up of 10 months, the combination regimen demonstrated potent antitumor activity:
- Progression-Free Survival (PFS): The median PFS for the 36 evaluable patients has not yet been reached. The 9-month PFS rate was 87.3%.
- Response Rates: The objective response rate (ORR) reached 52.8%, including 1 complete response (CR).
- Disease Control Rate (DCR): The DCR was 97.2%, with the vast majority of patients experiencing tumor shrinkage.
04 Safety Profile: Manageable Toxicity with No Unexpected Adverse Events
Safety data indicated that the combination of fruquintinib and serplulimab was generally well-tolerated and manageable:
- Common Treatment-Related Adverse Events (TRAEs): These primarily included rash, proteinuria, and hypertension.
- Severity: No Grade ≥4 adverse events (AEs) were observed. There were no treatment-related deaths.
- Treatment Continuity: No permanent treatment discontinuations occurred due to toxicity.
05 Prognostic Exploration: Sarcomatoid Features as a Potential Indicator of Rapid Progression
The researchers identified a significant biomarker signal: among the 36 evaluable patients, 3 experienced rapid disease progression within 4 months. Further analysis revealed that all 3 patients possessed sarcomatoid features. This finding suggests that sarcomatoid differentiation may be a key marker of resistance to this targeted-immune combination, providing a reference for future clinical research and patient stratification.
06 Conclusion and Outlook: A New Path for First-Line nccRCC Treatment
Dr. Jiwei Huang noted that fruquintinib plus serplulimab as a first-line treatment for metastatic or unresectable nccRCC demonstrated exceptional preliminary efficacy and a favorable safety profile. The high DCR and PFS rates underscore the potential of this regimen in managing this heterogeneous tumor type. The clinical trial is ongoing, and longer-term follow-up data with a larger sample size are expected to further validate its clinical application.
