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

NCT06182735 | Unknown Phase 1

• 1 other identifier: CGC729-IIT-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Renal Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Experiencing DLT

  1.Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) Dose limiting toxicity (DLT) is an AE that meets the following criteria and occurs within 28 days of CGC729 infusion.AE is graded according to CTCAE version 5.0.

  Day 28 after CGC729 infusion

Secondary Outcomes (6)

• ORR of CD70 CAR-NKT cell dynamics.

  Day 1 through week 52

• DCR of CD70 CAR-NKT cell dynamics.

  Day 1 through week 52

• The safey of CD70 CAR-NKT cell dynamics

  Day 1 through week 52

• Cmax of CD70 CAR-NKT cell dynamics.

  Day 1 through week 52

• Tmax of CD70 CAR-NKT cell dynamics.

  Day 1 through week 52

Study Arms (1)

Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

EXPERIMENTAL

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.

Combination Product: Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Interventions

Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells COMBINATION_PRODUCT

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

Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age 18 to 75 years.
• Patients with advanced clear cell renal cell carcinoma confirmed by histology or cytology to be recurrent or metastatic after at least second-line treatment.
• Archival and/or fresh tumor tissue samples are required.
• At least one measurable lesion at baseline per RECIST version 1.1.
• ECOG 0-1 points.
• The expected survival time is more than 12 weeks.
• 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.
• Pregnancy tests for women of childbearing age shall be negative, Both men and women agreed to use effective contraception.

You may not qualify if:

• Pregnant or lactating female subjects.
• Pregnant or lactating female subjects.
• Known positive test result for human immunodeficiency virus (HIV) oracquired immune deficiency syndrome (AIDS).
• Active infection or uncontrollable infection.
• Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, etc. .
• 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.
• Have a serious uncontrollable illness that may affect the subject receiving treatment for this study.
• 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.
• Subjects who are using systemic steroids or steroid inhalers for treatment.
• Use of anti-CD70 therapy or cell therapy within the previous 3 months.
• Immunotherapy, targeted drug therapy or chemotherapy within 5 drug half-lives within 2 weeks before cell infusion.
• Subjects allergic to immunotherapy or related drugs.
• Patients with leptomeningeal metastasis or central nervous system metastasis, and definite central nervous system underlying diseases with significant symptoms in the past 6 months.
• 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.
• Earnestly received or organ transplantation or preparing to receive organ transplants.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Jian Zhang

Shanghai, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; 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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Jian Zhang

  Fudan University

  PRINCIPAL INVESTIGATOR

• Dingwei Ye

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Zhang

CONTACT

18017312991; syner2000@163.com

Dingwei Ye

CONTACT

021-64175590; ydw@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Urology Department

Study Record Dates

• First Submitted: December 6, 2023
• First Posted: December 27, 2023
• Study Start: July 17, 2023
• Primary Completion: January 28, 2025
• Study Completion: January 28, 2025
• Last Updated: December 27, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)