FDA Grants Breakthrough Therapy Designation for Affinity Enhanced T-Cell Therapy in Synovial Sarcoma

On 9 February 2016, Adaptimmune Therapeutics plc announced that the US Food and Drug Administration (FDA) granted Breakthrough Therapy designation for its affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma. This designation applies to HLA-A201, HLA-A205, or HLA-A*206 allele-positive patients with inoperable or metastatic synovial sarcoma who have undergone prior chemotherapy and whose tumor expresses the NY-ESO-1 tumor antigen.

The Breakthrough Therapy designation was based on the outcomes of a phase I/II trial involving patients with unresectable, metastatic, or recurrent synovial sarcoma who had received prior chemotherapy. Patients were treated with lymphodepleting chemotherapy followed by immunotherapy with T-cells engineered to recognize an HLA-A2 restricted NY-ESO-1 peptide. The trial results, presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC), showed a 60% response rate among the 10 patients receiving the target dose of cells and a 50% overall response rate in the 12 patients receiving any dose of cells. Additionally, 90% of those who received the target dose and 75% of all patients were alive and under long-term follow-up.

The most common adverse events reported included nausea, anaemia, pyrexia, lymphophenia, and neutropenia. Cytokine release syndrome (CRS) was observed in four of twelve patients, with grade 3 CRS in two patients; no grade 4 CRS events were noted.

Adaptimmune plans to initiate pivotal studies with its affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma by the end of 2016 and is also exploring its development in myxoid round cell liposarcoma. The therapy is currently under investigation for myeloma, melanoma, ovarian cancer, and non-small cell lung cancer.

The Breakthrough Therapy designation, part of the FDA Safety and Innovation Act of 2012, aims to expedite the development and review of drugs for serious or life-threatening conditions. It requires preliminary clinical evidence indicating that the drug may offer substantial improvement over available therapies on at least one clinically significant endpoint. This designation provides all the benefits of the fast track program, including intensive FDA guidance, organizational commitment from senior managers, and eligibility for rolling and priority review of the company’s Biologic License Application.

Adaptimmune, a clinical-stage biopharmaceutical company, focuses on novel cancer immunotherapy products based on its T-cell receptor (TCR) platform. Its lead program, an affinity enhanced T-cell therapy targeting the NY-ESO cancer antigen, has shown efficacy and tolerability in phase I/II trials across various cancers. The company collaborates with GlaxoSmithKline for the development and commercialization of the NY-ESO TCR program and is advancing over 30 intracellular target peptides through its research programs.