NCT04729543

MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer

Adoptive Therapy With TCR Gene-engineered T Cells to Treat Patients With MAGE-C2-positive Melanoma and Head and Neck Cancer

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Erasmus Medical Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Single-centre, first-in-man phase I/II trial to demonstrate safety and efficacy of MAGE-C2/HLA-A2 TCR T cells (MC2 TCR T cells) in advanced melanoma (MEL) and head-and-neck carcinoma (HNSCC).

Detailed description

In this patient study, the investigators target the Cancer Germline Antigen (CGA) MAGE-C2 (MC2), and use T cells with a young phenotype. MC2 is highly expressed in melanoma (MEL) and head-and-neck squamous cell carcinoma (HNSSC), but not in healthy adult tissues. The investigators isolated MC2-specific TCRs from MEL patients who showed clinical responses following vaccination that were accompanied by significant frequencies of anti-MC2 CD8 T cells in blood and tumor without apparent side effects. Following extensive evaluation of in vitro anti-tumor and self-reactivities, the investigators have selected a TCR that recognizes the ALK epitope in the context of HLA-A2 for clinical development. Furthermore, preclinical studies showed that epigenetic pretreatment of tumor cells, but not normal cells, up-regulated MC2 gene expression and resulted in enhanced recognition of MC2 by the selected TCR. In parallel to the above studies, the investigators renewed their GMP protocol to process T cells, using stimulating antibodies and cytokines, to generate T cells with a young phenotype. In the current phase I/II study, the investigators explore the safety and anti-tumor efficacy of T cells engineered with the selected TCR in patients with MC2-positive MEL and HNSSC. The study contains the following unique elements: * CGA not targeted before by T cell therapy * New T cell processing method to generate young T cells * Pretreatment of patients with epigenetic drugs * No chemotherapy prior to T cell infusion Leads: * Clinical PI: Astrid van der Veldt, MD, PhD * Clinical logistics: Karlijn de Joode, MD * T cell production: Monique de Beijer, PhD; and Cor Lamers, PhD * Coordinator/Preclinical PI: prof. Reno Debets, PhD

Conditions

• Melanoma
• Melanoma, Uveal
• Head and Neck Cancer

Interventions

Type	Name	Description
BIOLOGICAL	Adoptive therapy with autologous MC2 TCR T cells	Adoptive therapy with autologous MC2 TCR T cells combined with AZA/VP

Timeline

• Start date: 2020-10-20
• Primary completion: 2024-12-20
• Completion: 2027-10-20
• First posted: 2021-01-28
• Last updated: 2023-12-04

Locations

1 site across 1 country: Netherlands