NCT05430555

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, 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

• Status: Terminated
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: T-knife GmbH · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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

Interventions

Type	Name	Description
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

Timeline

• Start date: 2022-07-29
• Primary completion: 2024-01-08
• Completion: 2024-01-08
• First posted: 2022-06-24
• Last updated: 2024-02-07

Locations

14 sites across 5 countries: Belgium, Germany, Netherlands, Spain, United Kingdom