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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 : June 24, 2022
Sponsor:
Information provided by (Responsible Party):
T-knife GmbH

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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
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
Official Title: 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
Estimated Study Start Date : June 2022
Estimated Primary Completion Date : June 2024
Estimated Study Completion Date : June 2037

Arm Intervention/treatment
Experimental: MAGE-A1 - directed TCR transduced autologous T-cells
Single-dose, intravenous infusion
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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05430555


Contacts
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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

Locations
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Belgium
University Hospital Ghent Recruiting
Ghent, Belgium, 9000
Contact: Liesbeth De Langhe       liesbeth.delanghe@uzgent.be   
Principal Investigator: Sylvie Rottey, MD         
Spain
Hospital Universitario Vall d´Hebrón Recruiting
Barcelona, Spain, 08035
Contact: Alba Silverio Pons       operationalnursing@vhio.net   
Principal Investigator: Elena Garralda, MD         
START Madrid-HM CIOCC Recruiting
Madrid, Spain, 28050
Contact: Irene Valderrama Sierra       irene.valderrama@startmadrid.com   
Principal Investigator: Emiliano Calvo, MD         
Sponsors and Collaborators
T-knife GmbH
Investigators
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Study Director: Eugen Leo, MD, PhD Chief Medical Officer
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Responsible Party: T-knife GmbH
ClinicalTrials.gov Identifier: NCT05430555    
Other Study ID Numbers: TK-8001-01
2021-004158-49 ( EudraCT Number )
First Posted: June 24, 2022    Key Record Dates
Last Update Posted: June 24, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by T-knife GmbH:
Advanced stage solid tumors
MAGE-A1
TCR-transgenic T-cells
Additional relevant MeSH terms:
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Neoplasms