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A Phase 1/2, First-in-Human, Open-Label, Two-Part Clinical Trial of TK-8001 in Patients With HLA-A*02:01 Genotype and Advanced-Stage/Metastatic MAGE-A1+ Solid Tumors (IMAG1NE)

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ClinicalTrials.gov Identifier: NCT05430555
Recruitment Status : Recruiting
First Posted : June 24, 2022
Last Update Posted : August 19, 2022
Sponsor:
Information provided by (Responsible Party):
T-knife GmbH

Tracking Information
First Submitted Date  ICMJE June 1, 2022
First Posted Date  ICMJE June 24, 2022
Last Update Posted Date August 19, 2022
Actual Study Start Date  ICMJE July 29, 2022
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 23, 2022)
  • Number of participants with treatment-emergent Adverse Events as assessed by CTCAE v5.0 (Part 1 of trial) [ Time Frame: Up to 15 years after TK-8001 treatment (52 weeks core follow-up, 14 years long-term follow up) ]
    Incidence and grade of treatment emergent adverse events and serious adverse events number and type of dose-limiting toxicities
  • Antitumoral activity of TK-8001 (Part 2 of trial) [ Time Frame: Up to 15 years after TK-8001 treatment, or until disease progression ]
    Evaluation of overall response rate, rate of stable disease, partial response, and complete response rates of TK-8001 monotherapy, according to RECIST Version 1.1 and iRECIST
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 23, 2022)
End of dose escalation [ Time Frame: 28 days after TK-8001 treatment of last patient in part 1 ]
RP2D will be determined through integrated evaluation of adverse events, serious adverse events, antitumoral activity, and evaluation of the biological and physiological effects of TK-8001 in the body.
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 A Phase 1/2, First-in-Human, Open-Label, Two-Part Clinical Trial of TK-8001 in Patients With HLA-A*02:01 Genotype and Advanced-Stage/Metastatic MAGE-A1+ Solid Tumors
Official Title  ICMJE A Phase 1/2, First-in-Human, Open-Label, Two Part Clinical Trial of TK-8001 (MAGE-A1--Directed TCR Transduced Autologous CD8+ T-cells) in Patients With HLA-A*02:01 Genotype and Advanced Stage/Metastatic, MAGE-A1+ Solid Tumors That Either Have No Further Approved Therapeutic Alternative(s) or Are in a Non-Curable State and Have Received a Minimum of Two Lines of Systemic Therapy
Brief Summary The aim of this study is to determine the safety, tolerability and anti-tumoral activity of autologous T cells transduced with a T cell receptor specific for MAGE-A1 in eligible patients with advanced solid tumors.
Detailed Description This is a Phase 1/2, first-in-human, open-label, two-part clinical trial of TK-8001 (MAGE-A1-directed TCR-transduced autologous CD8+ T-cells) in patients with HLA-A*02:01 genotype and advanced-stage/metastatic, MAGE-A1+ solid tumors that either have no further approved therapeutic alternative(s) or are in a non-curable state as per the Investigator's assessment and have received a minimum of two lines of systemic therapy. The trial will consist of a Phase 1 Part and a Phase 2 Part. In the Phase 1 Part (dose-escalation), at least 6 patients and up to 18 patients (if DLT occurs) will receive escalating doses of TK-8001. In the Phase 2 Part (expansion), up to 30 patients will receive TK-8001 to further evaluate the efficacy and safety of TK-8001 and to confirm the RP2D. Both the Phase 1 Part (dose-escalation) and Phase 2 Part (expansion) of the trial will consist of the following periods: Screening and Leukapheresis Period, Screening II, Conditioning Period, TK-8001 Treatment Period, DLT Monitoring Period, Core Follow-up Period (Year 1), Long-term Follow-up Period (Year 2 - 15).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
The trial will consist of a Phase 1 Part and a Phase 2 Part. After Phase 1 Part (dose-escalation) a Phase 2 Part (expansion) will follow. In total, up to 48 patients may receive TK-8001 to further evaluate the efficacy and safety of TK-8001 and to confirm the recommended phase 2 dose (RP2D).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Advanced Solid Tumors
Intervention  ICMJE Biological: Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR
Single-dose intravenous infusion of MAGE-A1 directed TCR-transgenic T cells following a conditioning chemotherapy
Study Arms  ICMJE Experimental: MAGE-A1 - directed TCR transduced autologous T-cells
Single-dose, intravenous infusion
Intervention: Biological: Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR
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: June 23, 2022)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2037
Estimated Primary Completion Date June 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Able to understand and comply with study procedures
  • At least 18 years old
  • Advanced-stage/metastatic, solid tumor malignancy with no further available approved therapeutic alternative(s) or in a non-curable state as per treating physician's assessment with the patient having received a minimum of two lines of approved systemic therapy
  • HLA-A*02:01 genotype.
  • MAGE-A1+ tumor positive for MAGE-A1
  • At least one measurable lesion, that can be accurately measured as per RECIST Version 1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
  • Life expectancy > 3 months as assessed by the Investigator
  • Adequate organ function
  • All toxicities related to prior therapy must have recovered to baseline or Grade ≤ 1 based on CTCAE v5.0
  • Immune-related adverse events (irAEs) from previous therapies must have recovered to baseline or Grade ≤ 1
  • Women of non-childbearing potential due to surgical sterilization or menopause
  • Women of childbearing potential must be using a highly effective method of contraception
  • Men with female partners of childbearing potential must use highly effective methods of contraception

Exclusion Criteria:

  • Any tumor-directed therapy within 14 days before start of conditioning therapy
  • Any other MAGE-A1-targeting therapy.
  • Pre-existing arrhythmia, uncontrolled angina pectoris, presently uncontrolled heart failure, or any myocardial infarction/coronary event as well as any thromboembolic event at any time < 6 months prior to screening.
  • Left ventricular ejection fraction (LVEF) < 45% as measured by an echocardiogram
  • History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (within 6 months prior to screening)
  • Active allergy requiring continuous systemic medication or active infections requiring IV/PO anti-infectious therapy
  • History of or clinical evidence of CNS primary tumors or metastases
  • Systemic steroids at a daily dose of > 5 mg of prednisolone, for the last 14 days prior to leukapheresis
  • Major surgery within last 4 weeks prior to consent
  • Known/expected hypersensitivity against TK-8001, DMSO, and/or other cellular therapy components.
  • Active disease/ongoing infection with HIV, HBV, HCV, TB, syphilis, or SARS-CoV-2
  • Any other diseases, or condition that in the opinion of the Investigator would contraindicate the use of the investigational product
  • Receipt of any organ transplantation, except for transplants that do not require immunosuppression
  • Any vaccine administration within 4 weeks of IP administration.
  • Patient is pregnant or breastfeeding
  • Known active drug or alcohol abuse
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Felix Lichtenegger, MD, PhD +49 151 70419904 felix.lichtenegger@t-knife.com
Contact: Ralf Wolter, PhD +49 175 4427208 ralf.wolter@t-knife.com
Listed Location Countries  ICMJE Belgium,   Germany,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05430555
Other Study ID Numbers  ICMJE TK-8001-01
2021-004158-49 ( EudraCT Number )
Has Data Monitoring Committee Yes
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 T-knife GmbH
Original Responsible Party Same as current
Current Study Sponsor  ICMJE T-knife GmbH
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Eugen Leo, MD, PhD Chief Medical Officer
PRS Account T-knife GmbH
Verification Date June 2022

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