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

Advanced Solid Tumors Clinical Trial

— IMAG1NE  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05430555
• Other study ID #: TK-8001-01
• Secondary ID: 2021-004158-49
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 29, 2022
• Est. completion date: January 8, 2024

Study information

• Verified date: February 2024
• Source: T-knife GmbH
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 23
• Est. completion date: January 8, 2024
• Est. primary completion date: January 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

Intervention

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

Locations

Country	Name	City	State
Belgium	Universite Libre de Bruxelles (ULB) - Institut Jules Bordet Anderlecht	Brussel
Belgium	Universite Catholique de Louvain (UCL) - Cliniques Universitaires Saint-Luc - Institut Roi Albert II	Brussels
Belgium	University Hospital Ghent	Ghent
Belgium	Centre Hospitalier Universitaire (CHU) de Liège	Liège
Germany	Charité - Universitätsmedizin Berlin - Campus Benjamin Franklin	Berlin
Germany	Technische Universität Dresden (TU Dresden)	Dresden	Sachsen
Germany	Universitatsklinikum Frankfurt, Goethe Universitat	Frankfurt
Germany	Klinikum der Universität München	Munich
Germany	Universitätsklinikum Würzburg	Würzburg
Netherlands	The Netherlands Cancer Institute	Amsterdam
Spain	Hospital Universitario Vall d´Hebrón	Barcelona
Spain	START Madrid-HM CIOCC	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
United Kingdom	The Christie NHS Foundation Trust	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
T-knife GmbH

Countries where clinical trial is conducted

Belgium,  Germany,  Netherlands,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Up to 15 years after TK-8001 treatment (1 year short-term follow-up, 14 years long-term follow up)
Primary	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)	Up to 15 years after TK-8001 treatment, or until disease progression
Secondary	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.	28 days after TK-8001 treatment of last patient in Phase 1