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

NCT ID: NCT05430555

Last Updated: 2024-02-07

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-07-29
• Study Completion Date: 2024-01-08

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, 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).

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NA
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MAGE-A1 - directed TCR transduced autologous T-cells

Single-dose, intravenous infusion

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 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
• 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

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, 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

T-knife GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Behzad K Masouleh, MD, PhD

Role: STUDY_DIRECTOR

T-knife GmbH

Locations

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

Brussels, , Belgium

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

Brussels, , Belgium

University Hospital Ghent

Ghent, , Belgium

Centre Hospitalier Universitaire (CHU) de Liège

Liège, , Belgium

Technische Universität Dresden (TU Dresden)

Dresden, Saxony, Germany

Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin

Berlin, , Germany

Universitatsklinikum Frankfurt, Goethe Universitat

Frankfurt, , Germany

Klinikum der Universität München

Munich, , Germany

Universitätsklinikum Würzburg

Würzburg, , Germany

The Netherlands Cancer Institute

Amsterdam, , Netherlands

Hospital Universitario Vall d´Hebrón

Barcelona, , Spain

START Madrid-HM CIOCC

Madrid, , Spain

Clínica Universidad de Navarra

Pamplona, , Spain

The Christie NHS Foundation Trust

Manchester, , United Kingdom

Countries

Belgium; Germany; Netherlands; Spain; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39038917 (View on PubMed)

Other Identifiers

2021-004158-49

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

TK-8001-01

Identifier Type: -

Identifier Source: org_study_id