Genetically engineered NY-ESO-1 specific T cells in HLA-A201+ patients with advanced cancers.

TPS3102

Background: NY-ESO-1 (CTAG-1B) is a cancer testis antigen associated with spontaneous and vaccine-induced immunity that can lead to improved clinical outcomes. NY-ESO-1 is not expressed in vital tissues, and is expressed in approximately 40% of ovarian, 60% of advanced myeloma, and 70% of synovial sarcoma tumors. Expression is correlated with tumor proliferation and high risk features. A human-derived affinity-optimized TCR that recognizes the NY-ESO-1 derived SLLMWITQC peptide in complex with HLA‐A*0201 (NY-ESO^c259) has been generated, and clinically tested as previously described using adoptive T cell transfer with supportive IL-2¹ Methods: Multiple clinical studies were initiated in HLA-A201+ patients with NY-ESO-1 expressing tumors. NY-ESO-1^c259-engineered autologous T-cells are manufactured centrally, using a 12 day commercial-grade closed system, and are administered without supportive IL-2. 40 patients have been infused: 25/26 on a phase I/II study in adults with systemic or multifocal myeloma requiring autologous stem cell transplantation, and who have incompletely responded to prior therapy or have high risk features (NCT01352286); 10/30 on a pilot study in patients ≥4 years old with unresectable, metastatic or recurrent synovial sarcoma (NCT01343043); 5/20 on a phase I study in adults with refractory or platinum resistant ovarian cancer and/or that have received ≥2 lines of chemotherapy (NCT01567891). Pre-infusion lymphodepleting chemotherapy is administered, and varies in intensity across studies. Primary objectives include safety and tolerability. Secondary objectives include evaluation of gene modified cells persistence in blood and tumor biopsies, lineage and functionality of these cells over time, and monitoring for serum cytokine levels and NY-ESO-1 antigen on tumor post infusion. Response assessments are performed using RECIST (sarcoma), IMWR criteria (myeloma), or immune-related response criteria (irRC; ovarian). 1. Robbins PF, Morgan RA, Feldman SA, et al: Tumor Regression in Patients With Metastatic Synovial Cell Sarcoma and Melanoma Using Genetically Engineered Lymphocytes Reactive With NY-ESO-1. Journal of Clinical Oncology 29:917-924, 2011 Clinical trial information: NCT01343043.