MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer — MC2TCR  

Head and Neck Cancer Clinical Trial

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

Status Recruiting

Clinical Trial 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).

Clinical Trial 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 ;

Related Conditions & MeSH terms

• Head and Neck Cancer
• Head and Neck Neoplasms
• Melanoma
• Melanoma, Uveal

• NCT number: NCT04729543
• Study type: Interventional
• Source: Erasmus Medical Center
• Contact: A.A.M. van der Veldt, MD, PhD
• Phone: +31 107041754
• Email: a.vanderveldt@erasmusmc.nl
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: October 20, 2020
• Completion date: October 20, 2027