Pucotenlimab Combination With Vorolanib as Neoadjuvant Therapy for ccRCC

Phase II Single-arm Clinical Study of the Efficacy and Safety of Pucotenlimab in Combination With Vorolanib Neoadjuvant Therapy for Patients With High-risk Renal Carcinoma Indicating Partial Nephrectomy

Through the neoadjuvant treatment with a combination of Pucotenlimab and Vorolanib, it enabled the successful and safe implementation of partial nephrectomy in patients with localized renal cancer, who had indications for nephron-sparing surgery but faced considerable difficulty in preserving the kidney (T1b with an endophytic component ≥75% or T2)

Study Overview

• Status: Recruiting
• Conditions: Neoadjuvant Therapy; Clear Cell Renal Cell Carcinoma (ccRCC); Vorolanib
• Intervention / Treatment: Drug: Pucotenlimab combination with Vorolanib

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiling Zhang, M.D; Phone Number: +862087342318; Email: zhangzhl@sysucc.org.cn
• Study Contact Backup: Name: Yulu Peng, M.D; Phone Number: +862087342318; Email: pengyl1@sysucc.org.cn

Study Locations

• China
  • Other (Non U.s.)
    • Guangzhou, Other (Non U.s.), China, 0755
      • Recruiting
      • Sun yat-sen University Cancer Center
      • Contact: Zhiling Zhang, M.D; Phone Number: +862087342318; Email: zhangzhl@sysucc.org.cn
      • Contact: Yulu Peng, M.D; Phone Number: +862087342318; Email: pengyl1@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign a written informed consent form (ICF).
2. Age at the time of enrollment is between 18 years old and 85 years old, regardless of gender.
3. The physical fitness score of the Eastern Cooperative Oncology Group (ECOG) in the United States is 0 or 1.
4. Expected survival period ≥ 3 months.
5. Preoperative biopsy pathology confirms renal clear cell carcinoma or renal cell carcinoma mainly composed of clear cell carcinoma
6. ECOG score 0 or 1
7. The patient is willing to undergo kidney preservation surgery
8. Preoperative assessment of healthy kidney GFR<60 ml/min through renal dynamic imaging
9. There are indications for kidney preservation surgery, but the surgery is difficult [① 4-7cm tumor located at the renal hilum or endogenous ≥ 75% (T1bN0M0); ② Tumors larger than 7cm (T2N0M0)] 9. There should be at least one measurable lesion (according to mRECIST v1.1 criteria) that is suitable for repeated and accurate measurements.
10. Good organ function, laboratory test results during the screening period meet the following criteria:

1. Hematology (no blood components or cell growth factors are allowed to support treatment within 2 weeks before starting treatment):

   a. Absolute neutrophil count (ANC) ≥ 1.5 × 109/L (1500/mm3); b. Platelet count (PLT) ≥ 100 × 109/L (100000/mm3); c. Hemoglobin (HB) ≥ 90 g/L;

2. Liver:

   1. Serum total bilirubin (TBIL) ≤ 1.5 × ULN;
   2. Alanine transaminase (ALT) and aspartate transaminase (AST) ≤ 2.5 × ULN; For subjects with liver metastasis, AST and ALT ≤ 5 × ULN
   3. Serum albumin (ALB) ≥ 28g/L

3. Coagulation function:

   International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN 11. The subjects are willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study.

   Exclusion Criteria:

   • Renal vein cancer thrombus

   • Diffuse tumor growth, with no clear boundary from normal renal parenchyma

   • General poor condition, anesthesia assessment cannot tolerate general anesthesia surgery

   • Have serious cardiovascular and cerebrovascular diseases, uncontrollable

   • hypertension and diabetes

   • Patients who have long-term use of immunosuppressants after organ transplantation

   • Patients who are currently using immunosuppressive drugs

   • Patients with clear infection or fever

   • Patients with T-cell lymphoma and myeloma

   • Patients who have concurrent malignant tumors, are currently undergoing treatment for other benign or malignant tumors, or have a history of other malignant tumors within the past six months

   • Metastatic renal cell carcinoma.

   • Received Chinese herbal medicine or immunomodulatory drugs with anti-tumor indications within 14 days prior to the first use of the investigational drug

   • Perform systematic treatment (including thymosin, interferon, interleukin, except for local use to control pleural effusion).

   • Suffering from active or potentially recurrent autoimmune diseases, except for vitiligo, hair loss, psoriasis, or eczema that do not require systemic treatment; Hypothyroidism caused by autoimmune thyroiditis only requires stable doses of hormone replacement therapy; Type I diabetes requiring only a stable dose of insulin replacement therapy.

   • Simultaneously enrolled in another clinical study, unless it is an observational, non interventional clinical study or a follow-up period of an interventional study.

   Known history of mental illness, drug abuse, alcoholism, or drug use.

   • Pregnant or lactating women.
   • Any past or current illness, treatment, or laboratory test abnormalities may confuse the research results, affect the full participation of the subjects in the study, or participation in the study may not be in the best interests of the subjects.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pucotenlimab combination with Vorolanib as neoadjuvant therapy; Vorolanib Treatment Vorolanib 200mg orally once daily, with or without food.Intravenous Infusion of Pucotenlimab(Injection) Infuse Pucotenlimab at a dose of 200mg intravenously every three weeks, constituting one treatment cycle, the maximum duration of treatment should not exceed 4 cycles.Perform imaging evaluation after 2 cycles, including renal CT plain scan+enhancement, measurement of tumor volume, and evaluation of ORR. If PD is detected in the first imaging assessment, the study will be terminated. According to the current diagnosis and treatment routine, communicate with the patient about the follow-up treatment plan:Radical nephrectomy; Utilization of other targeted therapies; Combination targeted therapy with immunotherapy. If the tumor shrinks significantly and the surgeon evaluates that partial nephrectomy can be safely performed, drug therapy should be stopped and partial nephrectomy should be performed; otherwise, continue treatment to 4 cycles before surgery.

Drug: Pucotenlimab combination with Vorolanib; 3.7.1 Vorolanib Vorolanib 200mg PO QD, taken with or without food. 3.7.2 Pucotenlimab Intravenous infusion of 200mg of Pucotenlimab (injection), once every 3 weeks, as one treatment cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) based on RECIST 1.1 criteria.	Evaluation at the end of Cycle 2 or Cycle 4 (each cycle is 21 days) of Pucotenlimab treatment

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): July 10, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 28, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): February 4, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Neoadjuvant therapy; Clear Cell Renal Cell Carcinoma (ccRCC); Vorolanib
• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Urologic Neoplasms; Carcinoma; Kidney Neoplasms; Carcinoma, Renal Cell; vorolanib
• Other Study ID Numbers: B2025-041-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No