US FDA accepts Adaptimmune's IND application for MAGE-A10 T candidate to treat NSCLC

The US Food and Drug Administration (FDA) has accepted Adaptimmune Therapeutics plc's Investigational New Drug (IND) application for autologous genetically modified T-cells expressing enhanced T cell receptors (TCRs) specific for MAGE A10 (MAGE-A10 T) in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), and that the IND is now active.

The acceptance of this IND allows Adaptimmune to initiate an open label phase I/II study designed to evaluate its wholly-owned MAGE-A10 T therapeutic candidate in NSCLC. Site initiation activities are now underway, and the company anticipates that enrolment will begin in 2015.

MAGE-A10 (melanoma antigen family A10) is a member of the MAGE-A family of cancer/testis tumour-associated antigens. It is believed to be expressed in approximately 30 per cent of lung (squamous cell carcinoma), bladder and skin melanomas, and at a lower incidence in many other cancers. Adaptimmune's proprietary technology enables the company to routinely generate TCRs which address intracellular targets, such as MAGE-A10, that are not accessible to certain other experimental modalities.

"The FDA's acceptance of this IND represents an important step in our strategy to identify and develop new T-cell-based immunotherapeutics to combat non-small cell lung cancer and other cancers, and we are excited to be working toward initiating clinical development of another of our promising TCR therapeutic candidates," said James Noble, Adaptimmune's chief executive officer. "In addition, this validates the progress we are making in applying our platform to develop a broad pipeline of novel proprietary TCR therapeutics."

This will be an open label phase I/II dose escalating study of three doses of genetically engineered MAGE-A10 T-cells in HLA-A 0201 and HLA-A02:06 patients with advanced (stage IIIB or stage IV) NSCLC whose tumors express this antigen. The study will assess the safety and tolerability of MAGE-A10 T in these patients. Secondary objectives will include the assessment of efficacy of MAGE-A10 T, measurements of durability of persistence of MAGE-A10 T-cells in the blood, and evaluations of the phenotype and functionality of MAGE-A10 T-cells.

Adaptimmune's proprietary TCR technology enables the company to genetically optimise T-cell receptors (TCR) in an effort to equip them to recognize and bind cancer antigens that are presented in small quantities on the surface of a cancer cell, whether of intracellular or extracellular origin, thus initiating cell death. The company's differentiated, proprietary technology allows it to reliably generate parental TCRs to naturally presented targets, affinity optimize its TCRs to bind cancer proteins from solid and hematologic cancers that are generally unavailable to naturally occurring TCRs, and to significantly reduce the risk of side effects resulting from off-target binding of healthy tissues.

Lung cancer is the third most common form of cancer in the US after prostate cancer in men and breast cancer in women. However, it is by far the leading cause of cancer deaths in both men and women in the United States. Non-small cell lung cancer or NSCLC is the most common type of lung cancer, representing approximately 85 per cent of lung cancers. The 1- and 5-year relative survival rates for lung cancer are 44 per cent and 17 per cent, respectively. More than half of lung cancer patients (57 per cent) are diagnosed at a late stage of cancer development, for which the 1- and 5-year survival is only 26 per cent and 4 per cent, respectively.

Adaptimmune is a clinical stage biopharmaceutical company focused on novel cancer immunotherapy products based on its T-cell receptor platform.