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Advanced Solid TumorsPhase 1/2IMAG1NENCT05430555

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

A Phase 1/2 study testing Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR in people with Advanced Solid Tumors, run by T-knife GmbH at 14 sites in 5 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Solid Tumors
What is being tested?
Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
14 sitesin 5 countries
Study dates
29 Jul 2022to 8 Jan 2024
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Able to understand and comply with study procedures
  • At least 18 years old
  • Phase 1 Part dose-escalation and Phase 1 Part expansion Cohort 1 only: Presence of an advanced-stage/metastatic, solid tumor in non-curable state as per current medical knowledge, for which there is either no further approved therapeutic alternative available or the subject is not eligible for them or, for which the subject has completed a minimum of two lines of approved systemic therapy in the advanced-stage/metastatic setting.
  • Phase 1 Part expansion Cohort 2 only: Presence of an advanced-stage/metastatic disease of the following indications: melanoma (skin or uveal), NSCLC, urothelial, breast cancer in non-curable state as per current medical knowledge, for which there is either no further approved therapeutic alternative available or the subject is not eligible for them or, for which the subject has completed a minimum of two lines of approved systemic therapy in the advanced-stage/metastatic setting.
  • HLA-A*02:01 genotype.
  • MAGE-A1+ tumor positive for MAGE-A1
Show all 11Show fewer
  • 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
  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • History of or clinical evidence of CNS primary tumors or metastases, unless they have been previously treated, and have been stable for at least 4 weeks prior to trial entry
  • Major surgery within last 4 weeks prior to consent
  • Active disease/ongoing infection with HIV, HBV, HCV, TB, syphilis, or SARS-CoV-2
  • Receipt of any organ transplantation, except for transplants that do not require immunosuppression
  • Any vaccine administration within 4 weeks of IP administration.

Trial locations and contacts

14 sites in 5 countries.

14 sites in 5 countries

Germany5 sites
  • Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin

    Berlin, 12203

  • Technische Universität Dresden (TU Dresden)

    Dresden, Saxony, 01304

  • Universitatsklinikum Frankfurt, Goethe Universitat

    Frankfurt, 60590

  • Klinikum der Universität München

    Munich, 81377

  • Universitätsklinikum Würzburg

    Würzburg, 97080

Other trials in Germany

Belgium4 sites
  • Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc - Institut Roi Albert II

    Brussels, 1000

  • Universite Libre de Bruxelles (ULB) - Institut Jules Bordet Anderlecht

    Brussels, 1000

  • University Hospital Ghent

    Ghent, 9000

  • Centre Hospitalier Universitaire (CHU) de Liège

    Liège, 4000

Other trials in Belgium

Spain3 sites
  • Hospital Universitario Vall d´Hebrón

    Barcelona, 08035

  • START Madrid-HM CIOCC

    Madrid, 28050

  • Clínica Universidad de Navarra

    Pamplona, 31008

Other trials in Spain

Netherlands1 site
  • The Netherlands Cancer Institute

    Amsterdam, 1066

Other trials in Netherlands

United Kingdom1 site
  • The Christie NHS Foundation Trust

    Manchester, M19 2WE

Other trials in United Kingdom

About this study

Official title: A Phase 1/2, First-in-Human, Open-Label, Accelerated-Titration, 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 Not Eligible for Them or Are in a Non- Curable State and Have Received a Minimum of Two Lines of Systemic Therapy

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.

Read the detailed description

This is a Phase 1/2, first-in-human, open-label, accelerated titration, two-part clinical trial of TK-8001 (MAGE-A1-directed TCR-transduced autologous CD8+ T-cells) in subjects with HLA-A*02:01 genotype and advanced stage/metastatic, MAGE-A1+ solid tumors (including but not limited to melanoma [skin or uveal], NSCLC, urothelial, breast, gastric [including gastroesophageal junction], esophageal, sarcoma, HNSCC, HCC, biliary tract, cervical, and salivary gland cancer) that either have no further approved therapeutic alternative or are not eligible for them or that are in a non-curable state as per the Investigator's assessment and have received a minimum of two lines of systemic therapy.

This two-part clinical trial will consist of a Phase 1 Part, which includes dose-escalation and expansion, and a Phase 2 Part.

In the Phase 1 Part dose-escalation, at least 6 subjects and up to 18 subjects (if DLT occurs) will receive escalating doses of TK-8001, with up to three dose levels explored. During the Phase 1 Part expansion, up to 20 additional subjects may be treated on DL3 if cleared during dose escalation to further evaluate the safety and efficacy of TK-8001 (Cohort 1).

An additional cohort of up to 10 subjects with brain metastases (Cohort 2) may also be treated on DL3 if cleared during dose-escalation. The maximum total number of subjects to be treated on DL3 during Phase 1 will be 33 subjects.

In the Phase 2 Part, 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 and Phase 2 Part of the trial will consist of the following periods: Screening and Leukapheresis Period, Conditioning Period, TK-8001 Treatment Period, DLT Monitoring Period, Short-term Follow-up Period (Year 1), and Long-term Follow-up Period (Year 2 - 15).

Being tested
Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR
Keywords
Advanced stage solid tumors, MAGE-A1, TCR-transgenic T-cells

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCRBiological

    Single-dose intravenous infusion of MAGE-A1 directed TCR-transgenic T cells following a conditioning chemotherapy

Study groups in NCT05430555
Study groupRoleWhat they receive
MAGE-A1 - directed TCR transduced autologous T-cellsExperimentalSingle-dose, intravenous infusion
Receives: Biological: Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability

    Incidence and grade of treatment-emergent adverse events (AEs) and serious adverse events (SAEs); Number and type of dose limiting toxicities (DLT)

    Measured: Up to 15 years after TK-8001 treatment (1 year short-term follow-up, 14 years long-term follow up)

  2. Preliminary anti tumor activity

    Evaluation of overall response rate (ORR), stable disease rate (SD), partial response rate (PR), and complete response (CR) rate of TK-8001 monotherapy, according to RECIST Version 1.1 and modified Response Evaluation Criteria in Solid Tumors (RECIST, V1.1) in cancer immunotherapy trials (iRECIST)

    Measured: Up to 15 years after TK-8001 treatment, or until disease progression

Secondary outcomes (1)
  1. End of dose escalation

    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.

    Measured: 28 days after TK-8001 treatment of last patient in Phase 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jun 2022
  2. Study start29 Jul 2022
  3. Primary completion8 Jan 2024
  4. Study completion8 Jan 2024

Why it stopped: Sponsor decision.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Sequential
Model description
This 2-part trial consists of Phase 1 dose-escalation and expansion and Phase 2. In escalation, 6-18 subjects will receive TK-8001 across 3 dose levels (DL). In expansion, subjects will be treated with the DL selected in escalation. Subjects without brain metastasis (Cohort 1) and subjects with brain metastases (Cohort 2) will both be included in expansion if DL3 is declared safe. Cohort 1 will include melanoma \[skin or uveal\], NSCLC, urothelial, breast, gastric esophageal, sarcoma, HNSCC, HCC, biliary tract, cervical, and salivary gland cancer subjects. Cohort 2 will only include melanoma \[skin or uveal\], NSCLC, urothelial, or breast cancer. In expansion, up to 20 additional subjects may be treated on DL3 if cleared during escalation. Up to 10 additional Cohort 2 subjects may be treated on DL3 if cleared during escalation. 33 subjects maximum may be treated on DL3 during Phase 1. If DL2 was safely completed the maximum total number of subjects to be treated on DL2 would be 12.
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05430555
Sponsor's protocol ID
TK-8001-01
Other IDs
2021-004158-49
Acronym
IMAG1NE
Status last verified
Feb 2024
First submitted
1 Jun 2022
Last updated
7 Feb 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Wermke M, Holderried TAW, Luke JJ, Morris VK, Alsdorf WH, Wetzko K, Andersson BS, Wistuba II, Parra ER, Hossain MB, Grund-Groschke S, Aslan K, Satelli A, Marisetty A, Satam S, Kalra M, Hukelmann J, Kursunel MA, Pozo K, Acs A, Backert L, Baumeister M, Bunk S, Wagner C, Schoor O, Mohamed AS, Mayer-Mokler A, Hilf N, Krishna D, Walter S, Tsimberidou AM, Britten CM. First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors. J Immunother Cancer. 2024 Jul 22;12(7):e008668. doi: 10.1136/jitc-2023-008668.

    PubMed 39038917

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Autologous CD8+ T-cells, transduced with MAGE-A1 directed TCR in people with Advanced Solid Tumors, run by T-knife GmbH at 14 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 7 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in Germany, Belgium, Spain, Netherlands, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Sponsor decision.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability (time frame: Up to 15 years after TK-8001 treatment (1 year short-term follow-up, 14 years long-term follow up)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05430555, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2024.

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