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.

Study Overview

• Status: Not yet recruiting
• Conditions: Clear Cell Renal Cell Carcinoma
• Intervention / Treatment: Drug: TQB2450 + Anlotinib

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 33
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: jiwei huang; Phone Number: 86-13651682825; Email: huangjiwie@renji.com

Participation Criteria

Eligibility Criteria

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

Description

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

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: 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 + 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Successful Nephron-Sparing Surgery	Defined as the proportion of patients who undergo partial nephrectomy	At the time of surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
MDT-Defined Conversion to Nephron-Sparing 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)	Assessed by RECIST v1.1	Pre-surgery
Pathologic Complete Response (pCR)	Pathologic Complete Response (pCR) after surgery	1 month after surgery
Renal Function Preservation	Proportion of patients with ≤20% decline in eGFR at 3 months postoperatively	3 month after surgery
Safety and Tolerability	Incidence of Grade ≥3 treatment-related adverse events (CTCAE v5.0)	enrollment to 90 days after surgery

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ctDNA methylation-based MRD dynamics across 4 time points	ctDNA methylation-based MRD dynamics across 4 time points	enrollment to 90 days after surgery
Tumor RNA expression and DNA methylation profiling	Tumor RNA expression and DNA methylation profiling	enrollment to 90 days after surgery

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Collaborators: Chinese PLA General Hospital; Huadong Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 31, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: May 15, 2026
• First Posted (Actual): May 22, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PD-L1; Nephron-Sparing Surgery; Neoadjuvant Therapy; Anlotinib; Clear Cell Renal Cell Carcinoma
• 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; anlotinib
• Other Study ID Numbers: SPARE-KIDNEY

Drug and device information, study documents

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