Neoadjuvant PD-L1 Inhibitor Plus Anlotinib for Kidney Preservation in Complex Renal Cell Carcinoma

Официальное название

Neoadjuvant PD-L1 Blockade Combined With Anlotinib to Enable Nephron-Sparing Surgery in Patients With High-Complexity Locally Advanced Clear Cell Renal Cell Carcinoma

Обзор

This is a prospective, multicenter, single-arm phase II study evaluating the efficacy and safety of neoadjuvant PD-L1 inhibitor TQB2450 in combination with anlotinib in patients with locally advanced, high-complexity (RENAL score ≥10) clear cell renal cell carcinoma (ccRCC). The primary objective is to determine whether neoadjuvant therapy can increase the rate of successful nephron-sparing surgery. In addition, this study incorporates a pre-specified translational research platform including circulating tumor DNA (ctDNA) methylation-based minimal residual disease (MRD) monitoring, tumor multi-omics profiling, and radiomics analysis. Artificial intelligence-based models will be developed to predict treatment response and surgical conversion, enabling precision neoadjuvant strategies.

Подробное описание

Patients with anatomically high-complexity locally advanced ccRCC (RENAL score ≥10) often require radical nephrectomy or technically challenging partial nephrectomy, resulting in increased perioperative risks and long-term renal function impairment. Evidence supporting neoadjuvant strategies in this specific high-complexity population remains limited.

This study evaluates a novel neoadjuvant approach combining PD-L1 blockade (TQB2450) with the multi-target tyrosine kinase inhibitor anlotinib. PD-L1 inhibition restores anti-tumor immunity, while antiangiogenic therapy promotes vascular normalization and enhances immune cell infiltration. This dual mechanism may improve tumor shrinkage and facilitate surgical conversion, particularly in central or hilar tumors.

Patients will receive 2-4 cycles of neoadjuvant therapy, followed by imaging assessment and multidisciplinary team (MDT) evaluation. Surgery will be performed within a predefined window after treatment completion.

A key translational component includes longitudinal ctDNA methylation-based MRD monitoring at four time points (baseline, after 2 cycles, pre-surgery, and post-surgery), combined with tumor tissue RNA expression and DNA methylation profiling, as well as radiomics feature extraction. These data will be integrated using machine learning algorithms to construct predictive models for treatment response and nephron-sparing surgery feasibility.

Вмешательства

• Препарат TQB2450 + Anlotinib
  Drug: TQB2450 (PD-L1 inhibitor) 1200 mg intravenously every 3 weeks Drug: Anlotinib 12 mg orally once daily (2 weeks on, 1 week off) Treatment duration: 2-4 cycles prior to surgery

Первичные конечные точки

• Rate of Successful Nephron-Sparing Surgery [Срок оценки: At the time of surgery]

Вторичные конечные точки (5)

• MDT-Defined Conversion to Nephron-Sparing Surgery [Срок оценки: Pre-surgery]
• Objective Response Rate (ORR) [Срок оценки: Pre-surgery]
• Pathologic Complete Response (pCR) [Срок оценки: 1 month after surgery]
• Renal Function Preservation [Срок оценки: 3 month after surgery]
• Safety and Tolerability [Срок оценки: enrollment to 90 days after surgery]

Критерии участия

Критерии включения

• • Age ≥18 years

• ECOG performance status 0-2
• Histologically confirmed clear cell renal cell carcinoma
• Clinical stage cT2-T3aN0M0 (AJCC 8th edition)
• RENAL nephrometry score ≥10
• Tumor assessed as requiring radical nephrectomy or complex partial nephrectomy
• Adequate organ function
• Signed informed consent

Критерии исключения

• • Prior systemic therapy for RCC (including ICIs or TKIs)

• Non-clear cell histology or sarcomatoid/rhabdoid differentiation >20%
• Active autoimmune disease requiring systemic therapy
• Active uncontrolled infection (HBV/HCV/HIV)
• Prior organ transplantation
• Uncontrolled cardiovascular or pulmonary disease
• Pregnancy or breastfeeding

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07602101 · SPARE-KIDNEY

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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