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MAGE-A4-directed TCR-T in the Treatment Amongst Subjects With 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: NCT06170294
Recruitment Status : Recruiting
First Posted : December 14, 2023
Last Update Posted : December 14, 2023
Sponsor:
Collaborator:
Shanghai Ming Ju Biotechnology Co., Ltd.
Information provided by (Responsible Party):
Shen Lin, Peking University

Tracking Information
First Submitted Date  ICMJE December 6, 2023
First Posted Date  ICMJE December 14, 2023
Last Update Posted Date December 14, 2023
Estimated Study Start Date  ICMJE January 1, 2024
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 6, 2023)
  • Rate of dose-limiting toxicities (DLTs) [ Time Frame: 28 days ]
    Dose-limiting toxicity (DLT) is defined as an adverse event that occurred within 28 days after JWTCR001 infusion that met any of the following criteria. Any Grade ≥3 non-hematologic toxicity associated with JWTCR001 that has not resolved to Grade ≤2 within 7 days, excluding clinically insignificant abnormalities in laboratory indicators. Grade ≥3 hematological toxicities. Grade ≥3 anaphylaxis. Grade ≥3 infection did not resolve to Grade ≤2 within 7 days after anti-infective treatment. Grade ≥3 autoimmune toxicity during treatment. Grade ≥3 cytokine release syndrome (CRS) during treatment that did not resolve to Grade ≤2 within 72 hours. Grade ≥3 TCR-T cell-associated encephalopathy syndrome/immune effector cell-associated neurotoxicity syndrome (CRES/ICANS) that did not resolve to Grade ≤2 within 72 hours. Grade 5 events of any nonmalignant cause.
  • Rate and severity of adverse events (AEs) and severe adverse events (SAEs) [ Time Frame: 2 years ]
    An AE is defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy can be determined.
  • Rate and severity of clinically-significant abnormalities in laboratory testings [ Time Frame: 2 years ]
    Clinically-significant abnormalities in laboratory testings.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: December 6, 2023)
  • Copy number of the vector transgene of JWTCR001 in peripheral blood [ Time Frame: 2 years ]
    The pharmacokinetic parameters of JWTCR001 will be evaluated by quantitative polymerase chain reaction (qPCR) for the copy number of the vector transgene of JWTCR001 in peripheral blood to evaluate T-cell expansion and persistence.
  • MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood [ Time Frame: 2 years ]
    The pharmacokinetic parameters of JWTCR001 will be evaluated by flow cytometry for the MAGE-A4 specific TCR+ T Cell concentration of JWTCR001 in peripheral blood to evaluate T cell expansion and persistence.
  • Antitumor efficacy-Progression-free survival (PFS) [ Time Frame: 2 years ]
    The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.
  • Antitumor efficacy-Duration of response (DOR) [ Time Frame: 2 years ]
    The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).
  • Antitumor efficacy-Time to response (TTR) [ Time Frame: 2 years ]
    The time from the first infusion to the first objective tumor response (tumor shrinkage of ≥30%) observed for patients who achieved a CR or PR.
  • Antitumor efficacy-Overall survival (OS) [ Time Frame: 2 years ]
    The period from the first infusion to any cause of death.
  • Antitumor efficacy-Objective response rate (ORR) [ Time Frame: 2 years ]
    The number of cases in which tumor size is reduced to complete response (CR) or partial response (PR) / the total number of evaluable cases (%). In the event of CR or PR, the subjects should confirm it no less than 4 weeks after the first evaluation.
  • Antitumor efficacy-Disease control rate (DCR) [ Time Frame: 2 years ]
    The number of cases in which response are achieved from the start of cell infusion/the total number of evaluable cases (%).
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 MAGE-A4-directed TCR-T in the Treatment Amongst Subjects With Advanced Solid Tumors
Official Title  ICMJE A Single-arm, Open-label, Dose Exploratory Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Autologous Humanized MAGE-A4-directed T Cell Receptor Engineered T Cell (JWTCR001) in Patients With Advanced Solid Tumors
Brief Summary A single-arm, open-label, dose exploratory study to evaluate the safety, efficacy, and pharmacokinetics of autologous humanized anti-MAGE-A4 T cell receptor-engineered T cell (TCR-T) in advanced solid tumors.
Detailed Description This study is a single-arm, open-label, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of T-cell receptor-engineered T cell (TCR-T) targeting melanoma-associated antigen-4 (MAGE-A4) and to obtain the preliminary efficacy results in subjects who have been diagnosed with advanced solid tumors with positive MAGE-A4 expression and refractory to prior standard systemic treatments.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumor
Intervention  ICMJE Drug: TCR-MAGE-A4 T-Cells
  • Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses
  • MAGE-A4-directed T cell receptor-engineered T Cells
Other Name: MAGE-A4-directed T cell receptor-engineered T Cells
Study Arms  ICMJE Experimental: TCR-MAGE-A4 T-Cells
The subjects enrolled will be sequentially assigned to the corresponding dose level.
Intervention: Drug: TCR-MAGE-A4 T-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: December 6, 2023)		 20
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2028
Estimated Primary Completion Date December 31, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. 18-75 year-old, male or female
  2. Voluntarily willing to participate in the study and sign the written informed consent form
  3. Life expectation ≥12 weeks
  4. European Cooperative Oncology Group (ECOG) ≤1 at screening, 24 hours prior to apheresis (APH), lymphodepletion (LD), and infusion
  5. Histologically-confirmed recurrent/metastatic advanced solid tumors
  6. Radiologically-confirmed progression disease after at least one prior line of systematic treatment and no available standard of care at screening, judged by investigators
  7. Fresh or formalin-fixed paraffin-embedded (FFPE) samples, immunohistochemistry (IHC)-stained MAGE-A4 positive
  8. Human leukocyte antigen (HLA)-A*02 allele matched
  9. Per response evaluation criteria in solid tumors (RECIST) version 1.1, at least one measurable lesion
  10. Adequate organ functions
  11. Adequate venous access for APH
  12. Non-hematological adverse events induced by previous treatment must have recovered to Grade ≤1 according to Common Terminology Criteria for Adverse Events (CTCAE), except for alopecia and peripheral neuropathy
  13. Women of childbearing potential must agree to use an effective and reliable contraceptive method during 28 days prior to lymphodepletion to 1 year post infusion; Male patients who have not undergone vasectomy and have sexual activity with women of childbearing potential must agree to the use of a barrier contraceptive method since lymphodepletion to 1 year post infusion, and sperm donation is prohibited during the study
  14. Women of childbearing potential must have negative serum human chorionic gonadotropin β (β-hCG) test result at screening and 48 hours prior to lymphodepletion

Exclusion Criteria:

  1. Pregnant or lactating women
  2. Human immunodeficiency virus (HIV) serology positive, or active hepatitis B virus (HBV)/hepatitis C virus (HCV)/Syphilis/Tuberculosis/ Coronavirus disease 2019 (COVID-19)
  3. Central nerve system (CNS) metastasis must have received treatment and been neurologically stable for ≥2 months, not requiring anti-seizure medications and off steroids for ≥ 1 month prior to APH
  4. Another primary malignancy within 3 years (with some exceptions for completely-resected early-stage tumors)
  5. Subjects with extensive metastases, or more rapid tumor progression prior to lymphodepletion in comparison to screening, etc. which might not be appropriate for further study treatment judged by the investigators
  6. Systematic autoimmune disorders requiring long-term systematic treatment
  7. Previously treated with any genetically engineered modified T cell therapy or other cell and gene therapy (CGT)
  8. History of organ transplant
  9. Uncontrolled or active infection within 72 hours prior to screening, APH, LD, or within 5 days prior to infusion
  10. Subjects with other serious diseases that may restrict them from participating in this study
  11. Clinically significant CNS disorders, such as epilepsy, stroke, Parkinson disease, etc
  12. Grade ≥ 2 hemorrhage within 30 days prior to screening, or in need of longterm anticoagulants
  13. Active digestive ulcer or gastrointestinal (GI) bleeding within 3 months prior to screening
  14. Not satisfying wash-out period for APH
  15. Previously allergic or intolerable to JWTCR001 or its components
  16. Unable or unwilling to comply with the study protocol, judged by the investigators
  17. Other situations implying that the subject might not be appropriate to participate in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Lin Shen 861088196561 linshenpku@163.com
Contact: Changsong Qi 861088196561 xiwangpku@126.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06170294
Other Study ID Numbers  ICMJE JWTCR001001
Has Data Monitoring Committee Not Provided
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: Yes
Current Responsible Party Shen Lin, Peking University
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Peking University
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Shanghai Ming Ju Biotechnology Co., Ltd.
Investigators  ICMJE
Principal Investigator: Lin Shen Peking University Cancer Hospital & Institute
PRS Account Peking University
Verification Date December 2023

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