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Study of Anti-5T4 CAR-NK Cell Therapy in Advanced Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05194709
Recruitment Status : Recruiting
First Posted : January 18, 2022
Last Update Posted : February 2, 2022
Sponsor:
Collaborator:
Imbioray (Hangzhou) Biomedicine Co., Ltd.
Information provided by (Responsible Party):
Wuxi People's Hospital

Tracking Information
First Submitted Date  ICMJE January 4, 2022
First Posted Date  ICMJE January 18, 2022
Last Update Posted Date February 2, 2022
Actual Study Start Date  ICMJE December 30, 2021
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 14, 2022)
Number of Adverse Events (AEs) [ Time Frame: From day 1 to day 90 after the last dose ]
To evaluate the safety and tolerability of anti-5T4 CAR-NK cells
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 14, 2022)
  • Objective response rate (ORR) [ Time Frame: Up to 1 year after infusion ]
    To determine the anti-tumor effectivity of anti-5T4 CAR-NK cells
  • Progression-free survival (PFS) [ Time Frame: Up to 1 year after infusion ]
    To determine the anti-tumor effectivity of anti-5T4 CAR-NK cells
  • Overall survival (OS) [ Time Frame: Up to 1 year after infusion ]
    To determine the anti-tumor effectivity of anti-5T4 CAR-NK cells
  • Disease control rate (DCR) [ Time Frame: Up to 1 year after infusion ]
    To determine the anti-tumor effectivity of anti-5T4 CAR-NK cells
  • Cytokine release [ Time Frame: Up to 1 year ]
    Blood samples will be collected at specified time points to detect the cytokine (IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, hsCRP) concentration (pg/mL)
  • Lymphocyte subtype [ Time Frame: Up to 1 year ]
    Blood samples will be collected at specified time points to analyze the lymphocyte subtypes (CD3, CD4, CD8, CD19, CD56)
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Anti-5T4 CAR-NK Cell Therapy in Advanced Solid Tumors
Official Title  ICMJE Clinical Trial of Anti-5T4 Oncofetal Trophoblast Glycoprotein (5T4) Conjugated Antibody Redirecting Natural Killer (CAR-NK) Cells in Advanced Solid Tumors
Brief Summary This study is an interventional, single arm, open-label, investigator-initiated trial (IIT) to evaluate the safety, tolerability, initial efficacy and pharmacokinetics (PK) of anti-5T4 CAR-NK cells in patients with advanced solid tumors.
Detailed Description The treatment cycle in this study is 21 days. The administration of CAR-NK cell will be performed on day 1 and day 3 of each cycle. Subjects will be treated continuously until the criteria for termination of treatment are met. In this study, the dose escalation design is adopted. The first administration dose in the first cycle is 3.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 4.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 4.0×10^9 cells.
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Biological: Anti-CAR-NK Cells
The administration of CAR-NK cell will be performed on day 1 and day 3 of each cycle (21 days). The first administration dose in the first cycle is 3.0×10^9 cells. If no adverse events were observed, the second administration dose in the first cycle would be 4.0×10^9 cells, and each administration dose in the second cycle and thereafter would be 4.0×10^9 cells.
Study Arms  ICMJE Experimental: Anti-5T4 CAR-NK Cells
Intervention: Biological: Anti-CAR-NK Cells
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 14, 2022)
40
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 30, 2022
Estimated Primary Completion Date December 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Subjects volunteer to participate in this clinical study, are fully aware of the study and have signed the Informed Consent Form (ICF). Subjects are willing to follow and able to complete all trial procedures.
  2. Age: adult at the age of 18-80 (both inclusive), female or male.
  3. Patients with advanced malignant solid tumors, histologically or cytologically confirmed, who had failed standard therapy, or had no standard therapy, or were not eligible for standard therapy at this stage; tumor biomarkers combined with imaging can be used to diagnose some special advanced tumors.
  4. Eastern Cooperative Oncology Group (ECOG) score ≤2 and expected survival time >3 months.
  5. Organ function during screening should meet the following criteria:

    • Absolute neutrophil count (ANC)≥0.8×109/L
    • Platelet (PLT)≥50×109/L
    • Hemoglobin (Hb)≥80g/L
    • Total bilirubin (TBIL)≤2×ULN
    • Alanine aminotransferase (ALT)≤3×ULN; Patients with liver metastasis or liver cancer: ≤5×ULN
    • Aspartate aminotransferase (AST)≤3×ULN; Patients with liver metastasis or liver cancer: ≤5×ULN
    • Creatinine (Cr)≤1.5× ULN
    • Creatinine clearance (Ccr) (to be calculated only when Cr > 1.5× ULN)>50ml/min/1.73m2 (Cockcroft-Gault formula)
    • Activated partial thrombin time (APTT)≤1.5×ULN
    • International normalized ratio (INR)≤1.5×ULN
  6. Subjects of reproductive age and their partners should agree to have no family planning and to use effective contraceptive methods (hormonal or barrier methods or abstinence, etc.) for 6 months from signing the ICF until the last dose of the study drug is administered; women of reproductive age should not be pregnant or breastfeeding.

Exclusion Criteria:

  1. Have received systemic antitumor therapy, including chemotherapy, immunotherapy, and radical radiotherapy, within 1 week prior to their first use of the study drug.
  2. Have participated in other clinical trials and received any unmarketed investigational drug or treatment within 4 weeks prior to first use of the study drug.
  3. Any prior adoptive cellular immunotherapy.
  4. Have undergone major organ surgery (excluding needle biopsy or surgery related to this indication) within 4 weeks prior to their first use of the study drug, or required elective surgery during the study period.
  5. Patients with severe infections that cannot be controlled.
  6. Patients with a known history of human immunodeficiency virus (HIV) infection, or a history of organ transplantation.
  7. Have active autoimmune diseases or have had autoimmune diseases that are likely to recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.). Except in the following cases: type 1 diabetes that was well controlled with hormone replacement therapy, hypothyroidism, skin conditions that did not require systemic therapy (e.g., vitiligo), and other conditions that were well controlled and that the investigator determined were less likely to recur (e.g., childhood asthma in remission).
  8. Have a history of serious cardiovascular and cerebrovascular diseases, including but not limited to:

    • There are serious cardiac rhythm or conduction abnormalities, such as ventricular arrhythmia, and Ⅱ-Ⅲ degree atrioventricular block, which need clinical intervention;
    • The mean QT interval corrected by Fridericia method (QTcF) is prolonged (male>450ms, female>470ms);
    • Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or other grade 3 or above cardiovascular and cerebrovascular events occurring within 6 months before the first administration;
    • Patients with heart failure or left ventricular ejection fraction (LVEF) < 50% in the New York Heart Association (NYHA) classification ≥II;
    • Hypertension beyond clinical control.
  9. Adverse effects of previous antineoplastic therapy have not returned to CTCAE grade 5.0≤2 (except for toxicity that the investigator determined to be of no safety risk, such as alopecia, hypothyroidism stabilized by hormone replacement therapy).
  10. Central nervous system metastases with clinical symptoms.
  11. Had other malignant tumors in the past 3 years, excluding skin basal cell carcinoma, ductal carcinoma in situ and cervical carcinoma in situ with a radical surgery.
  12. Have a history of alcohol or drug abuse or mental disorder.
  13. The investigator considered that the subjects had a history of other serious systemic diseases or other reasons that made them unsuitable for the study.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Peihua Lu, MD +8613583991399 lyzlyylxm@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05194709
Other Study ID Numbers  ICMJE IBR854-T01
WX-IBR-8 ( Other Identifier: Wuxi People's Hospital )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Wuxi People's Hospital
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Wuxi People's Hospital
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Imbioray (Hangzhou) Biomedicine Co., Ltd.
Investigators  ICMJE
Principal Investigator: Peihua P Lu, MD Wuxi People's Hospital
PRS Account Wuxi People's Hospital
Verification Date January 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP