FDA Grants Breakthrough Therapy Designation for Affinity Enhanced T-cell Therapy Targeting NY-ESO in Synovial Sarcoma
It is intended for patients with inoperable or metastatic synovial sarcoma who have received prior chemotherapy
On 9 February, 2016 Adaptimmune Therapeutics plc, a company specialised in the use of TCR engineered T-cell therapy to treat cancer, announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation for the affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma for HLA-A*201, HLA-A*205 or HLA-A*206 allele-positive patients with inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose tumour expresses the NY-ESO-1 tumour antigen.
The company is committed to investigating the potential of their NY-ESO-1 T cell therapy across a variety of cancers. The company stated that it is pleased that the FDA has granted Breakthrough Therapy designation for their T-cell therapy in synovial sarcoma, recognising both the unmet need for patients suffering from this disease as well as the promise of early data. They look forward to working closely with the FDA to expedite the clinical development of this therapeutic candidate.
The Breakthrough Therapy designation was based on the results of a phase I/II trial in patients with unresectable, metastatic or recurrent synovial sarcoma who have 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. Data from this study were most recently presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC) in November 2015.
In the primary efficacy analysis, 60% of the 10 patients receiving the target dose of cells responded, and there was a 50% overall response rate in the 12 patients receiving any dose of cells. The 90% (9/10) of those patients who received the target dose and 75% (9/12) of all patients were alive and on long term follow-up.
The most common adverse events included nausea, anaemia, pyrexia, lymphophenia and neutropenia. Cytokine release syndrome (CRS) was seen in four of twelve patients, with grade 3 CRS observed in two patients; no grade 4 CRS events were observed.
Adaptimmune recently announced that it will aim to initiate pivotal studies with its affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma around year end 2016, and that it will also explore development in myxoid round cell liposarcoma. Studies with this therapy are also underway in myeloma, melanoma, ovarian cancer and non-small cell lung cancer.
The breakthrough therapy designation was enacted as part of the FDA Safety and Innovation Act of 2012 and is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for breakthrough therapy designation require preliminary clinical evidence that demonstrates the drug may have substantial improvement on at least one clinically significant endpoint over available therapy. According to the FDA, breakthrough therapy designation conveys all of the fast track programme features, more intensive FDA guidance on an efficient drug development programme, an organisational commitment involving senior managers, and eligibility for rolling review and priority review of the company’s Biologic License Application when submitted.
Adaptimmune is a clinical stage biopharmaceutical company focused on novel cancer immunotherapy products based on its T-cell receptor (TCR) platform. Adaptimmune’s lead programme is an affinity enhanced T-cell therapy targeting the NY-ESO cancer antigen. Its NY-ESO TCR affinity enhanced T-cell therapy has demonstrated signs of efficacy and tolerability in phase I/II trials in solid tumours and in haematologic malignancies, including synovial sarcoma and multiple myeloma. Adaptimmune has a strategic collaboration and licensing agreement with GlaxoSmithKline for the development and commercialisation of the NY-ESO TCR programme. In addition, Adaptimmune has a number of proprietary programmes. The company has identified over 30 intracellular target peptides preferentially expressed in cancer cells and is currently progressing 12 through unpartnered research programmes. Adaptimmune has over 200 employees and is located in Oxfordshire, UK and Philadelphia, USA.
The company stated that their press-release contains forward-looking statements.