Comparing the Combination of Sullumab and Fruquintinib in Postoperative Adjuvant Therapy for High Recurrence Risk Non Transparent Renal Cell Carcinoma

A Randomized Controlled, Multicenter Phase III Clinical Study Comparing the Combination of Sullimumab and Fruquintinib in Postoperative Adjuvant Therapy for High Recurrence Risk Non Transparent Renal Cell Carcinoma

This study is testing a new treatment approach for people who have had surgery to remove a type of kidney cancer called non-clear cell renal cell carcinoma (non-ccRCC). This kind of kidney cancer is different from the most common type and tends to come back after surgery, especially in high-risk patients.

After surgery, many patients are at risk of their cancer returning. Right now, there is no standard treatment to prevent this from happening. This study aims to find out if combining two medications-Serplulimab (a PD-1 inhibitor) and Fruquintinib (a targeted drug that blocks blood vessel growth in tumors)-can help reduce the chance of cancer coming back.

The study will include up to 40 adults aged 18 to 75 who have had surgery to remove the tumor and are at high risk of recurrence. All participants will receive both drugs as part of an adjuvant therapy, meaning it is given after surgery to lower the risk of cancer returning.

Serplulimab will be given by IV every three weeks. Fruquintinib will be taken orally daily, with a schedule of 3 weeks on and 1 week off.

Treatment will last up to 12 months. Participants will be closely monitored throughout the study with regular check-ups, blood tests, imaging scans (like CT or MRI), and safety assessments. The main goal is to see how long patients stay free of cancer (called "disease-free survival"). Other goals include checking how well the treatment works, how safe it is, and whether certain biomarkers (like PD-L1 levels or genetic changes in tumor DNA) can predict who benefits most.

All medical care related to the study-including visits, scans, lab tests, and the study drugs-will be provided at no cost to participants. Participants may also have access to advanced molecular testing through a partner laboratory.

This is a single-center, open-label study, meaning everyone involved knows which treatment is being used. There is no placebo group; all participants receive active treatment.

The study team believes this combination could offer a promising way to improve outcomes for people with high-risk non-ccRCC after surgery. If successful, it may lead to a new standard of care for this patient group.

Participation is voluntary. Patients can leave the study at any time without affecting future medical care. Risks include side effects from the drugs, such as fatigue, high blood pressure, diarrhea, or immune-related reactions. The research team will monitor these carefully and provide appropriate care.

This study is being conducted by researchers at a single hospital in China and supported by domestic pharmaceutical companies. It follows all national and international guidelines for ethical research involving human participants.

It is hoped that this study will help better understand how to prevent kidney cancer from returning and improve survival for patients.

Inclusion Criteria:

• Age between 18 and 75 years, inclusive.
• Histologically confirmed diagnosis of non-clear cell renal cell carcinoma (non-ccRCC), including papillary, chromophobe, collecting duct, or other non-clear cell subtypes.
• Completed radical nephrectomy (open or laparoscopic) with no evidence of residual tumor by imaging or pathology.
• High-risk features defined as one or more of the following: pT3 or higher, regional lymph node involvement (N1), sarcomatoid differentiation, tumor necrosis, Fuhrman/ISUP nuclear grade ≥3, or positive surgical margin.
• ECOG performance status of 0 or 1.
• Adequate organ function: neutrophils ≥1.5 × 10⁹/L, platelets ≥100 × 10⁹/L, hemoglobin ≥9 g/dL; total bilirubin ≤1.5 × ULN; ALT/AST ≤2.5 × ULN; creatinine clearance ≥50 mL/min; INR ≤1.5.
• No prior adjuvant or neoadjuvant systemic anti-tumor therapy.
• Willing and able to provide written informed consent and comply with study procedures.

Exclusion Criteria:

• Pathological diagnosis of clear cell renal cell carcinoma or mixed histology with ≥20% clear cell component.
• Evidence of distant metastasis (M1) at baseline.
• History of active autoimmune disease (e.g., lupus, rheumatoid arthritis, inflammatory bowel disease) or current use of immunosuppressive agents.
• Uncontrolled hypertension (systolic >150 mmHg or diastolic >100 mmHg), significant cardiovascular disease, or uncontrolled heart failure.