Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Head and Neck Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anticonvulsants

Central Nervous System Depressants

Psychotropic Drugs

Analgesics

Azacitidine

Valproic Acid

Interleukin-2

Antimetabolites

Enzyme Inhibitors

Analgesics, Non-Narcotic

Neurotransmitter Agents

* Accelerated titration phase I design and a subsequent single arm phase II study
* Prior to T cell transfer (day 0), patients will be treated with valproic acid (dose 50 mg/kg/d, 7d; days -9 to day -3) and 5' azacytidine (dose 75mg/m2/d, 7d; days -9 to day -3)
* Phase I: patients will be treated with one single intravenous administration of MC2 TCR T cells at 5 different escalated doses of 5x10E7, 5x10E8, 5x10E9,1.0x10E10, and the total number of cultured TCR T cells (i.e., usually 1.0-5.0 x10E10 TCR T cells). MC2 TCR T cell infusions will be supported by low dose of IL-2 administrations (s.c. 5x10E5 IU/m2 2qd for 5 days)
* T cells will be processed using IL-15 and IL-21 to generate young T cells

Adoptive therapy with autologous MC2 TCR T cells combined with AZA/VP

Adoptive therapy with autologous MC2 TCR T cells

A.A.M. van der Veldt, MD, PhD

R. Debets, PhD, Prof

R. Debets, PhD, Prof.

Karlijn de Joode, MD

Monique de Beijer, PhD

Cor Lamers, PhD

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).

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

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

MTD is determined using an accelerated titration phase with T cell doses as described in treatment arm; AEs are recorded according to CTCAE 5.0

Anti-tumor responses are recorded according to RECIST v1.1 using the MTD from outcome 1

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer	NCT04729543	Melanoma Melanoma, Uveal Head and Neck C...	Adoptive therap...	18 Years -	Erasmus Medical Center
MAGE-C2 TCR T Cell Trial to Treat Melanoma and Head and Neck Cancer	NCT04729543	Melanoma Melanoma, Uveal Head and Neck C...	Adoptive therap...	18 Years -	Erasmus Medical Center

Spots Global Cancer Trial Database for adoptive therapy with autologous mc2 tcr t cells