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.
연구 개요
상세 설명
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.
연구 유형
등록 (추정된)
단계
- 2 단계
연락처 및 위치
연구 연락처
- 이름: jiwei huang
- 전화번호: 86-13651682825
- 이메일: huangjiwie@renji.com
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
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
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 해당 없음
- 중재 모델: 단일 그룹 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
|
실험적: 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
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Rate of Successful Nephron-Sparing Surgery
기간: At the time of surgery
|
Defined as the proportion of patients who undergo partial nephrectomy
|
At the time of surgery
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
MDT-Defined Conversion to Nephron-Sparing Surgery
기간: 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)
기간: Pre-surgery
|
Assessed by RECIST v1.1
|
Pre-surgery
|
|
Pathologic Complete Response (pCR)
기간: 1 month after surgery
|
Pathologic Complete Response (pCR) after surgery
|
1 month after surgery
|
|
Renal Function Preservation
기간: 3 month after surgery
|
Proportion of patients with ≤20% decline in eGFR at 3 months postoperatively
|
3 month after surgery
|
|
Safety and Tolerability
기간: enrollment to 90 days after surgery
|
Incidence of Grade ≥3 treatment-related adverse events (CTCAE v5.0)
|
enrollment to 90 days after surgery
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
ctDNA methylation-based MRD dynamics across 4 time points
기간: 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
기간: enrollment to 90 days after surgery
|
Tumor RNA expression and DNA methylation profiling
|
enrollment to 90 days after surgery
|
공동 작업자 및 조사자
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
추가 관련 MeSH 약관
기타 연구 ID 번호
- SPARE-KIDNEY
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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