Neoadjuvant Immune-based Combinations in Patients Undergoing Nephrectomy for Locally Advanced ccRCC

Study Overview
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Brief Summary
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The objective of this single-center clinical trial was to evaluate the objective response rate and safety of Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib， etc.) in neoadjuvant treatment of（T2a-T4NanyM0 or TanyN1M0） clear cell renal cell carcinoma.

Detailed Description
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The objective of this single-center clinical trial was to evaluate the objective response rate and safety of Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib，etc.) in neoadjuvant treatment of（T2a-T4NanyM0 or TanyN1M0） clear cell renal cell carcinoma.Toripalimab is a new antibody that may help activate the immune system by blocking the function of the inhibitory molecule PD-1. This is a single-institution, single-arm Phase 2 clinical trial. Patients will be treated with Toripalimab in combination with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib， etc.) and patients will undergo partial or radical nephrectomy after neoadjuvant therapy.

Official Title
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Phase II Trial of Neoadjuvant Immune-based Combinations in Patients Undergoing Nephrectomy for Locally Advanced ccRCC

Conditions
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Neoplasms, Kidney Neoplasms, Urologic Neoplasms, Urogenital Neoplasms, Female Urogenital Diseases, Urogenital Diseases, Kidney Diseases, Urologic Diseases, Male Urogenital Diseases, Carcinoma, Carcinoma, Renal Cell, Antineoplastic Agents, Immune Checkpoint Inhibitors

Intervention / Treatment
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* Drug: Toripalimab
* Drug: Axitinib
* Drug: Lenvatinib
* Drug: Sunitinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Imaging is consistent with（T2a-T4NanyM0 or TanyN1M0) clear cell renal cell carcinoma Puncture pathological biopsy was consistent with clear cell renal cell carcinoma Subjects were to undergo radical nephrectomy or partial nephrectomy or enucleation of renal tumor ECOG 0-1 points -Normal hematopoietic and organ function -- Understand and plan visits, treatments, laboratory tests, and other research procedures. Exclusion Criteria: Prior systemic anti-tumor treatment for RCC Patients who are receiving any other investigational agents. Clinical status indicating that immediate surgery (within 6 weeks) iswarranted regardless of whether neoadjuvant therapy is to beadministered, as assessed by the treating surgeon. Inability to undergo baseline tumor biopsy. Active or prior documented autoimmune or immunocompromisingconditions. Uncontrolled hypertension In the investigator's judgment, the subject has a medical history or current evidence of any disease, treatment, or laboratory abnormality that could confuse the results of the trial, interfere with the subject's participation throughout the trial, or is not in the subject's best interest to participate in the trial.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Subjects received Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib, Lenvatinib, Sunitinib,) followed by enucleation of renal tumor or partial nephrectomy or radical nephrectomy. | Drug: Toripalimab<br>* 240mg, IV (in the vein) on on day 1 of 3-week, 6-week and 9-week for a total of 3 doses prior to partial nephrectomy or radical nephrectomy<br>* Other names: anti-PD-1 monoclonal antibody;Drug: Axitinib<br>* 5 mg by mouth twice each day for 12 weeks prior to nephrectomy<br>* Other names: CLS-AX;Drug: Lenvatinib<br>* 18 mg by mouth once each day for 12 weeks prior to nephrectomy<br>* Other names: Lenvatinib mesylate (USAN);Drug: Sunitinib<br>* Subjects will receive a 21-day cycle of oral 50mg once a day for 14 days and then rest for 7days, requiring 4 cycles for a total of 12 weeks<br>* Other names: Sunitinib malate (JAN/USAN);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate of neoadjuvant treatment of (T2a-T4NanyM0 or TanyN1M0) clear cell renal cell carcinoma with Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib，etc.). | Tumor response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1). | week 12 of neoadjuvant treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of neoadjuvant treatment of clear cell renal cell carcinoma with Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib， etc.). | Safety as assessed by number of participants experiencing adverse events. | up to 90 days after end of treatment | 
| Marginal negative (R0) rate of （T2a-T4NanyM0 or TanyN1M0）clear cell renal cell carcinoma treated with Toripalimab combined with TKI (such as Axitinib，Lenvatinib，Sunitinib， etc.). | Marginal negative (R0) rate as assessed by number of participants experiencing Marginal negative (R0). | Baseline to date of surgery | 
| Disease-free survival (DFS) in（T2a-T4NanyM0 or TanyN1M0） clear cell renal cell carcinoma treated with Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib，etc.) neoadjuvant therapy. | DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first. | Up to 5 years after surgery | 
| Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor | Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry. | Baseline to date of surgery | 
| Change From Baseline in Regulatory T-cells (Tregs) in the Tumor | Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry. | Baseline to date of surgery | 
| Change From Baseline in CD4+ T-cells in the Tumor | Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry. | Baseline to date of surgery | 
| Change From Baseline in CD8+ T-cells in the Tumor | Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry. | Baseline to date of surgery | 
| Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor | Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean ratio of Type 1 to Type 2 tumor associated macrophages using immunohistochemistry. | Baseline to date of surgery | 
| Change From Baseline of Selected Cytokines in Peripheral Blood | Cytokines measured in peripheral blood were soluble CD27 (sCD27), eotaxin, macrophage inflammatory protein 1b (MIP-1b), and soluble programmed cell death protein 1 (sPD-1). | Baseline to Day 43 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ccRCC