Pucotenlimab Combination With Vorolanib as Neoadjuvant Therapy for ccRCC

Official title

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

Overview

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)

Interventions

• 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.

Primary outcome measures

• Objective Response Rate (ORR) based on RECIST 1.1 criteria. [Time frame: Evaluation at the end of Cycle 2 or Cycle 4 (each cycle is 21 days) of Pucotenlimab treatment]

Eligibility criteria

Inclusion criteria

• Voluntarily sign a written informed consent form (ICF).
• Age at the time of enrollment is between 18 years old and 85 years old, regardless of gender.
• The physical fitness score of the Eastern Cooperative Oncology Group (ECOG) in the United States is 0 or 1.
• Expected survival period ≥ 3 months.
• Preoperative biopsy pathology confirms renal clear cell carcinoma or renal cell carcinoma mainly composed of clear cell carcinoma
• ECOG score 0 or 1
• The patient is willing to undergo kidney preservation surgery
• Preoperative assessment of healthy kidney GFR<60 ml/min through renal dynamic imaging
• 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.
• Good organ function, laboratory test results during the screening period meet the following criteria:

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• 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;

• Liver:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun Yat-sen University Cancer Center — Guangzhou

Identifiers

NCT: NCT07386158 · B2025-041-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗