Neoadjuvant PD-L1 Inhibitor Plus Anlotinib for Kidney Preservation in Complex Renal Cell Carcinoma
Neoadjuvant PD-L1 Blockade Combined With Anlotinib to Enable Nephron-Sparing Surgery in Patients With High-Complexity Locally Advanced Clear Cell Renal Cell Carcinoma
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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- フェーズ2
連絡先と場所
研究連絡先
- 名前：jiwei huang
- 電話番号：86-13651682825
- メール：huangjiwie@renji.com
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
Inclusion Criteria:
• 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
Exclusion Criteria:
• 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
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：Neoadjuvant TQB2450 + Anlotinib
Neoadjuvant 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
|
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
|
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Rate of Successful Nephron-Sparing Surgery
時間枠：At the time of surgery
|
Defined as the proportion of patients who undergo partial nephrectomy
|
At the time of surgery
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
MDT-Defined Conversion to Nephron-Sparing Surgery
時間枠：Pre-surgery
|
o Defined as conversion from pre-treatment planned radical nephrectomy or complex partial nephrectomy to post-treatment feasibility of standard or simplified partial nephrectomy；o Determined by a centrally reviewed multidisciplinary team based on imaging
|
Pre-surgery
|
|
Objective Response Rate (ORR)
時間枠：Pre-surgery
|
Assessed by RECIST v1.1
|
Pre-surgery
|
|
Pathologic Complete Response (pCR)
時間枠：1 month after surgery
|
Pathologic Complete Response (pCR) after surgery
|
1 month after surgery
|
|
Renal Function Preservation
時間枠：3 month after surgery
|
Proportion of patients with ≤20% decline in eGFR at 3 months postoperatively
|
3 month after surgery
|
|
Safety and Tolerability
時間枠：enrollment to 90 days after surgery
|
Incidence of Grade ≥3 treatment-related adverse events (CTCAE v5.0)
|
enrollment to 90 days after surgery
|
その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
ctDNA methylation-based MRD dynamics across 4 time points
時間枠：enrollment to 90 days after surgery
|
ctDNA methylation-based MRD dynamics across 4 time points
|
enrollment to 90 days after surgery
|
|
Tumor RNA expression and DNA methylation profiling
時間枠：enrollment to 90 days after surgery
|
Tumor RNA expression and DNA methylation profiling
|
enrollment to 90 days after surgery
|
協力者と研究者
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- SPARE-KIDNEY
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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