Adaptimmune initiates Phase I/II T-cell therapy study in NSCLC

Adaptimmune has initiated a Phase I/II study of its affinity enhanced T-cell therapy targeting the MAGE-A10 cancer antigen in patients with locally advanced or metastatic (Stage IIIb or IV) non-small cell lung cancer (NSCLC).

This will be the first study of Adaptimmune’s unpartnered affinity enhanced T-cell therapy targeting MAGE-A10, a highly immunogenic member of the MAGE-A family of cancer testis antigens. MAGE-A10 is expressed in a number of solid tumour cell types, and the immunogenicity of the MAGE-A10 antigen has been robustly established. Cancer testis antigen expression in cancer is often associated with higher grade tumours.

“The initiation of this study is an important step in our goal to identify and develop new T-cell-based immunotherapeutics to combat non-small cell lung cancer and other cancers, and we are excited to initiate clinical development of another of our promising affinity enhanced TCR therapeutic candidates,” said Dr Rafael Amado, Adaptimmune’s Chief Medical Officer. “We have already seen encouraging clinical responses in certain cancers to our lead T-cell therapeutic candidate, which targets the NY-ESO-1 cancer antigen, demonstrating that it is possible to utilise our proprietary affinity enhancement technology to modify TCRs to so that they target cancer cells effectively. It is our hope that we may one day offer patients suffering from non-small cell lung cancer an efficacious and well-tolerated therapeutic option.”

Trial will assess the safety and tolerability of the T-cell therapy

This is an open label, 3+3 dose escalation study of autologous T-cells genetically engineered with an affinity optimised MAGE-A10 TCR in HLAA*0201 and HLA-A*0206 positive patients with stage IIIb or stage IV NSCLC expressing the MAGE-A10 antigen. Though the prevalence of HLA sub-types varies from population to population, the most common in the western world is HLA-A2. Among the HLA-A2 variants, the most prevalent are HLA-A*0201 and HLA-A*0206.

The study is intended to enroll up to 32 patients in leading clinical centers located in the United States and Europe and will assess the safety and tolerability of Adaptimmune’s affinity enhanced T-cell therapy targeting MAGE-A10. Secondary objectives will include the assessment of clinical efficacy, measurements of durability of persistence of MAGE-A10 T-cells in the blood, and exploratory tumour biomarker studies and evaluations of the phenotype and functionality of MAGE-A10 T-cells.