IMAG1NE: 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
Study Details
Study Description
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 |
|---|---|---|
|
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).
Study Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Number of participants with treatment-emergent Adverse Events as assessed by CTCAE v5.0 (Part 1 of trial) [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) [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
- End of dose escalation [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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Able to understand and comply with study procedures
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At least 18 years old
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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
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HLA-A*02:01 genotype.
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MAGE-A1+ tumor positive for MAGE-A1
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At least one measurable lesion, that can be accurately measured as per RECIST Version 1.1
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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Life expectancy > 3 months as assessed by the Investigator
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Adequate organ function
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All toxicities related to prior therapy must have recovered to baseline or Grade ≤ 1 based on CTCAE v5.0
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Immune-related adverse events (irAEs) from previous therapies must have recovered to baseline or Grade ≤ 1
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Women of non-childbearing potential due to surgical sterilization or menopause
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Women of childbearing potential must be using a highly effective method of contraception
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Men with female partners of childbearing potential must use highly effective methods of contraception
Exclusion Criteria:
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Any tumor-directed therapy within 14 days before start of conditioning therapy
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Any other MAGE-A1-targeting therapy.
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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.
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Left ventricular ejection fraction (LVEF) < 45% as measured by an echocardiogram
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History of CNS disease such as stroke, seizure, encephalitis, or multiple sclerosis (within 6 months prior to screening)
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Active allergy requiring continuous systemic medication or active infections requiring IV/PO anti-infectious therapy
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History of or clinical evidence of CNS primary tumors or metastases
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Systemic steroids at a daily dose of > 5 mg of prednisolone, for the last 14 days prior to leukapheresis
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Major surgery within last 4 weeks prior to consent
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Known/expected hypersensitivity against TK-8001, DMSO, and/or other cellular therapy components.
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Active disease/ongoing infection with HIV, HBV, HCV, TB, syphilis, or SARS-CoV-2
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Any other diseases, or condition that in the opinion of the Investigator would contraindicate the use of the investigational product
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Receipt of any organ transplantation, except for transplants that do not require immunosuppression
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Any vaccine administration within 4 weeks of IP administration.
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Patient is pregnant or breastfeeding
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Known active drug or alcohol abuse
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospital Ghent | Ghent | Belgium | 9000 | |
| 2 | University Hospital C.-G.-Carus | Dresden | Sachsen | Germany | 01304 |
| 3 | Charité - University Medicine Berlin - Campus Benjamin Franklin | Berlin | Germany | 12203 | |
| 4 | Hospital Universitario Vall d´Hebrón | Barcelona | Spain | 08035 | |
| 5 | START Madrid-HM CIOCC | Madrid | Spain | 28050 |
Sponsors and Collaborators
- T-knife GmbH
Investigators
- Study Director: Eugen Leo, MD, PhD, Chief Medical Officer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- TK-8001-01
- 2021-004158-49