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

A Phase I Clinical Study to Assess the Safety and Efficacy of CD70-targeted CAR-NKT in the Treatment of Relapsed or Metastatic Advanced Renal Cell Carcinoma.

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

Study Overview

• Status: Recruiting
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Combination product: Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 9
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jian Zhang; Phone Number: 18017312991; Email: syner2000@163.com
• Study Contact Backup: Name: Dingwei Ye; Phone Number: 021-64175590; Email: ydw@163.com

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Jian Zhang
    • Contact: Jian Zhang; Phone Number: 18017312991; Email: syner2000@163.com
    • Contact: Dingwei Ye; Phone Number: 021-64175590; Email: ydw@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Combination product: Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells; Biological: CD70 CAR-NKT cells. Drug: Cyclophosphamide. Drug: Fludarabine.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR of CD70 CAR-NKT cell dynamics.	Assess Objective response rate(ORR)	Day 1 through week 52
DCR of CD70 CAR-NKT cell dynamics.	Disease control rate (DCR)	Day 1 through week 52
The safey of CD70 CAR-NKT cell dynamics	Adverse events (AEs) of CD70 CAR-NKT cell dynamics, Duration and severity of AEs,AE is graded according to CTCAE version 5.0.	Day 1 through week 52
Cmax of CD70 CAR-NKT cell dynamics.	Peak Plasma Concentration	Day 1 through week 52
Tmax of CD70 CAR-NKT cell dynamics.	Time to Maximum Plasma Concentration	Day 1 through week 52
AUC of CD70 CAR-NKT cell dynamics.	Area under the plasma concentration versus time curve	Day 1 through week 52

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Jian Zhang, Fudan University; Principal Investigator: Dingwei Ye, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2023
• Primary Completion (Estimated): January 28, 2025
• Study Completion (Estimated): January 28, 2025

Study Registration Dates

• First Submitted: December 6, 2023
• First Submitted That Met QC Criteria: December 26, 2023
• First Posted (Estimated): December 27, 2023

Study Record Updates

• Last Update Posted (Estimated): December 27, 2023
• Last Update Submitted That Met QC Criteria: December 26, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Carcinoma, Renal Cell; Carcinoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide; Fludarabine
• Other Study ID Numbers: CGC729-IIT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No