CD70-targeted CAR-NKT Cells(CGC729) Therapy in the Renal Cell Carcinoma

NCT ID: NCT06182735

Last Updated: 2023-12-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-07-17

Study Completion Date

2025-01-28

Brief Summary

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This is a phase I, open-label, single-arm study conducted to evaluate the safety, tolerability, PK, and preliminary efficacy of CGC729 with Relapsed or Metastatic advanced renal cell carcinoma.

Condition or disease:Renal Cell Carcinoma Intervention/treatment: Biological: CD70 CAR-NKT cells Phase 1

Detailed Description

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Dose exploration for this study will be a 3+3 design with a target DLT rate of \<1/3. A particular dose level will be expanded to 6 patients if one patient out of 3 patients treated at that particular dose level develops DLT. Once this occurs, further dose-escalations are halted until the dose has proven to be safe in the expanded cohort. If 2 or more in a cohort of 6 patients develop DLT no further dose escalation is allowed, and the next lower dose level will be expanded to 6 patients in total. The highest dose among the dose levels tested at which no more than one out of six patients experiences DLT will be considered the MTD. Dose exploration can be discontinued once one or more dose levels with an acceptable safety profile and satisfactory antitumor activity have been selected for subsequent evaluation.

During the treatment period of the study, three dose levels of CGC729 will be evaluated. Each of the dose levels will evaluate the safety of the CAR-NKT cells.

Conditions

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Renal Cell Carcinoma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Lymphodepleting regimen, Cyclophosphamide 250mg/m2 IV on day -5 to -3 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of CAR-NKT on day 0.

Potential CGC729 doses:

Dose level 1: 5.0×106 CAR- NKT cells/m2; Dose level 2: 1.5×107 CAR- NKT cells/m2; Dose level 3: 4.5×107 CAR- NKT cells/m2.

Group Type EXPERIMENTAL

Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Intervention Type COMBINATION_PRODUCT

Biological: CD70 CAR-NKT cells. Drug: Cyclophosphamide. Drug: Fludarabine.

Interventions

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Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Biological: CD70 CAR-NKT cells. Drug: Cyclophosphamide. Drug: Fludarabine.

Intervention Type COMBINATION_PRODUCT

Eligibility Criteria

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Inclusion Criteria

1. Subjects or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.
2. Age 18 to 75 years.
3. Patients with advanced clear cell renal cell carcinoma confirmed by histology or cytology to be recurrent or metastatic after at least second-line treatment.
4. Archival and/or fresh tumor tissue samples are required.
5. At least one measurable lesion at baseline per RECIST version 1.1.
6. ECOG 0-1 points.
7. The expected survival time is more than 12 weeks.
8. The functions of important organs are basically normal: Hematopoietic function: neutrophils 1.5×109/L, platelets 75×109/L, hemoglobin 80g/L; Renal function: creatinine clearance of ≥60 mL/min.; Liver function: ALT and AST≤2.5×ULN (≤5 × ULN for patients with liver metastases); Total bilirubin≤1.5×ULN. Coagulation INR \< 1.7.
9. Pregnancy tests for women of childbearing age shall be negative, Both men and women agreed to use effective contraception.

Exclusion Criteria

1. Pregnant or lactating female subjects.
2. Pregnant or lactating female subjects.
3. Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS).
4. Active infection or uncontrollable infection.
5. Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, etc. .
6. Having a history of any mental illness, including dementia, altered mental status, which may affect informed consent and the understanding of the subject by the relevant questionnaire.
7. Have a serious uncontrollable illness that may affect the subject receiving treatment for this study.
8. Subjects with other malignant tumors within the past 2 years, except basal or squamous skin cancer, superficial bladder cancer, and breast cancer in situ, have been completely cured and do not need follow-up treatment.
9. Subjects who are using systemic steroids or steroid inhalers for treatment.
10. Use of anti-CD70 therapy or cell therapy within the previous 3 months.
11. Immunotherapy, targeted drug therapy or chemotherapy within 5 drug half-lives within 2 weeks before cell infusion.
12. Subjects allergic to immunotherapy or related drugs.
13. Patients with leptomeningeal metastasis or central nervous system metastasis, and definite central nervous system underlying diseases with significant symptoms in the past 6 months.
14. Subjects with NYHA heart failure class ≥2 or hypertension uncontrolled by standard therapy requiring special treatment, previous history of myocarditis, or myocardial infarction within 6 months.
15. Earnestly received or organ transplantation or preparing to receive organ transplants.
16. Other investigators deem it unsuitable to participate in the study.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fudan University

OTHER

Sponsor Role lead

Responsible Party

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Ding-Wei Ye

Head of Urology Department

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Jian Zhang

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Dingwei Ye

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Locations

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Jian Zhang

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jian Zhang

Role: CONTACT

Phone: 18017312991

Email: [email protected]

Dingwei Ye

Role: CONTACT

Phone: 021-64175590

Email: [email protected]

Facility Contacts

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Jian Zhang

Role: primary

Dingwei Ye

Role: backup

Other Identifiers

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CGC729-IIT-01

Identifier Type: -

Identifier Source: org_study_id