Clinical Study of CD70-targeted CAR-T Therapy for Advanced/Advanced Renal Cancer

NCT05420519 | Unknown Phase 1

• 1 other identifier: PBC036
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I clinical study to evaluate the safety and tolerability of CAR-T in patients with advanced/metastatic renal cell carcinoma, and to obtain the maximum tolerated dose of CAR-T and phase II Recommended dose.

Conditions

Metastatic Tumor; Renal Cell Carcinoma; Advanced Cancer

Keywords

CAR-T; CD70

Outcome Measures

Primary Outcomes (2)

• Incidence of Adverse events after CD70 CAR-T cells infusion [Safety and Tolerability]

  Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)

  28 days

• Obtain the maximum tolerated dose of CD70 CAR-T cells[Safety and Tolerability]

  Dose-limiting toxicity after cell infusion

  28 days

Secondary Outcomes (9)

• Disease control rate of CAR-T cell preparations in CD70 positive advanced malignancies [Effectiveness]

  3 months

• Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]

  3 months

• Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]

  3 months

• Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]

  2 years

• Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]

  2 years

Other Outcomes (5)

• The correlation between CD70 positive rate and safety

  2 years

• Correlation between CD70 positive rate and efficacy

  2 years

• Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]

  2 years

Study Arms (1)

CD70-targeted CAR-T

EXPERIMENTAL

Infusion of CD70-targeted CAR-T cells by dose of 1-10x106 cells/kg

Biological: CD70 CAR-T cells

Interventions

CD70 CAR-T cells BIOLOGICAL

Administration method: intravenous infusion； Subjects will be treated with Fludarabine and Cyclophosphamide before cell infusion.

CD70-targeted CAR-T

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥18 years old, male or female;
• Diagnosed with advanced/metastatic renal cell carcinoma (staging according to 2017AJCC) by histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimens), and the tumor is positive for CD70 expression (positive for tumor CD70 confirmed by histology or pathology) (IHC 3+));
• At least after TKI, anti-vascular drug treatment is ineffective, there is no available standard treatment plan or standard treatment fails or cannot tolerate (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.) no effective treatment;
• Measurable and evaluable lesions specified by RECIST version 1.1: Measurable disease is defined as at least one lesion that can be accurately measured on at least one level (long diameter needs to be recorded); ), each lesion must be \>10mm when measured by Magnetic Resonance Imaging (MRI), The lymph node must be \>15mm in the short axis;
• ECOG 0-2 points (Appendix 2);
• The expected survival time is more than 12 weeks;
• No serious mental disorder;
• The functions of important organs are basically normal:
• Hematopoietic function: neutrophils 1.0×109/L, platelets 75×109/L, hemoglobin 80g/L;
• Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
• Renal function: serum creatinine≤2.0×ULN;
• Liver function: ALT and AST ≤2.0×ULN (for patients with liver tumor infiltration, it can be relaxed to ≤3.0×ULN);
• Total bilirubin ≤2.0×ULN (Gilbert syndrome or combined liver tumor infiltration can be relaxed to ≤3.0×ULN);
• Oxygen saturation \> 92% in non-oxygen state.
• Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;

You may not qualify if:

• Those who have received CAR-T therapy or other gene-modified cell therapy before screening;
• Received anti-CD70 drug treatment before screening;
• Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;
• Received any of the following treatments before screening:
• Participated in other interventional clinical studies before screening, including: the last use of unmarketed new drugs is less than 3 months from the time of cell reinfusion, or the last use of marketed drugs is less than 5 months from the time of cell reinfusion half-life;
• Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is shorter) before apheresis;
• Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to apheresis (inhalation or topical is allowed in the absence of active autoimmune disease Use steroids and adrenal corticosteroid replacement at doses greater than 10 mg/day of prednisone);
• Received live attenuated vaccine within 4 weeks before screening;
• Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;
• Patients with other malignancies other than renal cancer within 3 years before screening, except for the following cases: malignant tumors that have received radical treatment, and no known active disease within ≥3 years before enrollment; or Treated non-melanoma skin cancer with no evidence of disease;
• Suffering from any of the following heart diseases:
• New York Heart Association (NYHA) stage III or IV congestive heart failure;
• Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
• Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
• History of severe nonischemic cardiomyopathy.

Sponsors & Collaborators

• Chongqing Precision Biotech Co., Ltd: lead

Study Sites (1)

The Second People's Hospital of Shandong Province

Jinan, Shandong, 250000, China

RECRUITING

MeSH Terms

Conditions

Neoplasm Metastasis; Carcinoma, Renal Cell

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Jianfeng Bi, M.D

  The Second People's Hospital of Shandong Province

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jingwang Bi, M.D

CONTACT

13066029387; jingwangbi@live.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2022
• First Posted: June 15, 2022
• Study Start: December 31, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: August 18, 2023

Record last verified: 2023-08

Locations

CN (1)