A Clinical Research About CD70-targeted CAR-NKT Cells Therapy Advanced Malignant Solid Tumors

This is a phase I, open-label, single-arm study conducted to evaluate the efficacy, safety and PK of CGC729 in the treatment of advanced malignant solid tumors.

Condition or disease:advanced malignant solid tumors. Intervention/treatment:Biological: CD70 CAR-NKT cells. Phase:I

Study Overview

• Status: Recruiting
• Conditions: Solid Tumor
• Intervention / Treatment: Combination product: Cyclophosphamide + Fludarabine + Infusion of CAR-NKT Cells

Detailed Description

This was a dose-expansion study, we plan to enroll 6 to 12 patients with CD70-positive advanced malignant solid tumors to CGC729 treatment. The intended enrollment for the evaluation of treatment efficacy and safety was planned to be 3 to 6 patients per tumor type.

We used leukapheresis for cell collection. The lymphodepletion procedure was conducted using a combination of fludarabine and cyclophosphamide.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jian Zhang; Phone Number: 18017312991; Email: syner2000@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China
      • Recruiting
      • Fudan University
      • Contact: Jian Zhang; Phone Number: 18017312991; Email: syner2000@163.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 18 to 75 years.
• ECOG 0-1 points.
• The expected survival time is more than 3 months.
• Patients with advanced advanced malignant solid tumor confirmed by histology or cytology to be recurrent or metastatic after at least second-line treatment.
• IHC: CD70 positive.
• At least one measurable lesion at baseline per RECIST version 1.1.
• 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.Prothrombin time (PT) : INR < 1.7.

• Pregnancy tests for women of childbearing age shall be negative, Both men and women agreed to use effective contraception.
• 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.

Exclusion Criteria:

• Use of cell therapy within the previous one month.
• Risk of severe bleeding in esophageal cancer
• 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.
• Patients with leptomeningeal metastasis or central nervous system metastasis, and definite central nervous system underlying diseases with significant symptoms in the past 6 months.
• Immunotherapy, targeted drug therapy or chemotherapy within 5 drug half-lives within 2 weeks before cell infusion.
• Active hepatitis B, HIV positive and HCV positive
• Active infection or uncontrollable infection.
• 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.
• Unstable respiratory diseases, including interstitial pneumonia.
• Uncontrolled ascites and pleural effusion
• Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, etc. .
• Subjects who are using systemic steroids or steroid inhalers for treatment.
• Pregnant or lactating female subjects.
• 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;	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
ORR of CD70 CAR-NKT cell dynamics	Assess Objective response rate	Day 1 through week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DCR of CD70 CAR-NKT cell dynamics	Disease control rate	Day 1 through week 56
DOR of CD70 CAR-NKT cell dynamics	Duration of Response	Day 1 through week 56
PFS of CD70 CAR-NKT cell dynamics	Progress Free Survival	Day 1 through week 56
OS of CD70 CAR-NKT cell dynamics	Overall survival	Day 1 through week 56

Collaborators and Investigators

• Sponsor: Fudan University
• Investigators: Principal Investigator: Jian Zhang, Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2024
• Primary Completion (Estimated): June 28, 2026
• Study Completion (Estimated): June 28, 2026

Study Registration Dates

• First Submitted: April 28, 2024
• First Submitted That Met QC Criteria: April 30, 2024
• First Posted (Actual): May 1, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 30, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; 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-02

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