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

Sponsor

Jinling Hospital, China (Other)

Overall Status

Recruiting

CT.gov ID

NCT06114940

Collaborator

(none)

Enrollment

Location

Arm

36.4

Anticipated Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
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	Drug: Toripalimab Drug: Axitinib Drug: Lenvatinib Drug: Sunitinib	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

32 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Dec 20, 2022

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Experimental group 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 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 Other Names: anti-PD-1 monoclonal antibody Drug: Axitinib 5 mg by mouth twice each day for 12 weeks prior to nephrectomy Other Names: CLS-AX Drug: Lenvatinib 18 mg by mouth once each day for 12 weeks prior to nephrectomy Other Names: Lenvatinib mesylate (USAN) Drug: Sunitinib 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 Other Names: Sunitinib malate (JAN/USAN)

Arm

Intervention/Treatment

Experimental: Experimental group

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

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

Other Names:

anti-PD-1 monoclonal antibody

Drug: Axitinib

5 mg by mouth twice each day for 12 weeks prior to nephrectomy

Other Names:

CLS-AX

Drug: Lenvatinib

18 mg by mouth once each day for 12 weeks prior to nephrectomy

Other Names:

Lenvatinib mesylate (USAN)

Drug: Sunitinib

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

Other Names:

Sunitinib malate (JAN/USAN)

Outcome Measures

Primary Outcome Measures

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.). [week 12 of neoadjuvant treatment]
Tumor response rate according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Secondary Outcome Measures

Safety of neoadjuvant treatment of clear cell renal cell carcinoma with Toripalimab combined with tyrosine kinase inhibitors TKI (such as Axitinib，Lenvatinib，Sunitinib， etc.). [up to 90 days after end of treatment]
Safety as assessed by number of participants experiencing adverse events.
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.). [Baseline to date of surgery]
Marginal negative (R0) rate as assessed by number of participants experiencing Marginal negative (R0).
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. [Up to 5 years after surgery]
DFS was defined as the time from date of surgery to disease recurrence or death whichever occurred first.
Change From Baseline in Myeloid-derived Suppressor Cells (MDSCs) in the Tumor [Baseline to date of surgery]
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean MDSCs using immunohistochemistry.
Change From Baseline in Regulatory T-cells (Tregs) in the Tumor [Baseline to date of surgery]
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean Tregs using immunohistochemistry.
Change From Baseline in CD4+ T-cells in the Tumor [Baseline to date of surgery]
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD4+ T-cells using immunohistochemistry.
Change From Baseline in CD8+ T-cells in the Tumor [Baseline to date of surgery]
Tumor tissue was collected from study biopsies and surgical samples, and was used to assess mean CD8+ T-cells using immunohistochemistry.
Change From Baseline in Ratio of Type 1 to Type 2 Tumor Associated Macrophages in the Tumor [Baseline to date of surgery]
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.
Change From Baseline of Selected Cytokines in Peripheral Blood [Baseline to Day 43]
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).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.