FDA Grants Breakthrough Therapy Designation to Adaptimmune's T-Cell Therapy for Synovial Sarcoma
Key Insights
The FDA granted Breakthrough Therapy designation to Adaptimmune's affinity-enhanced T-cell therapy targeting NY-ESO for synovial sarcoma (search), expediting its development.
The designation was based on Phase I/II trial results showing a 60% response rate in patients receiving the target dose of engineered T-cells.
Adaptimmune's therapy targets HLA-A*201, HLA-A*205, or HLA-A*206 allele-positive patients with inoperable or metastatic synovial sarcoma (search).
Adaptimmune Therapeutics plc (Nasdaq:ADAP) has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for its affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma (search). This designation aims to expedite the development and review of the therapy for patients with HLA-A201, HLA-A205 or HLA-A*206 allele-positive inoperable or metastatic synovial sarcoma who have received prior chemotherapy and whose tumors express the NY-ESO-1 (search) tumor antigen.
The Breakthrough Therapy designation, enacted as part of the Food and Drug Administration Safety and Innovation Act of 2012, is reserved for drugs demonstrating substantial improvement over available therapies on at least one clinically significant endpoint. It provides Adaptimmune with all the features of the fast track program, including more intensive FDA guidance, organizational commitment involving senior managers, and eligibility for rolling review and priority review of the Biologic License Application.
Clinical Trial Data
The designation was supported by data from a Phase I/II trial involving patients with unresectable, metastatic, or recurrent synovial sarcoma (search) who had previously undergone chemotherapy. The trial involved lymphodepleting chemotherapy followed by immunotherapy with T-cells engineered to recognize an HLA-A2 restricted NY-ESO-1 (search) peptide.
Data presented at the 2015 Annual Meeting of the Society of Immunotherapy for Cancer (SITC) showed promising results. In the primary efficacy analysis, 60% of the 10 patients receiving the target dose of cells demonstrated a response. The overall response rate in the 12 patients receiving any dose of cells was 50%. Furthermore, 90% of patients receiving the target dose and 75% of all patients were alive during long-term follow-up.
Safety Profile
The most common adverse events observed in the trial included nausea, anemia, pyrexia, lymphopenia, and neutropenia. Cytokine release syndrome (CRS) was observed in four of the twelve subjects, with grade 3 CRS occurring in two subjects. No grade 4 CRS events were reported.
Future Development
Adaptimmune plans to initiate pivotal studies with its affinity enhanced T-cell therapy targeting NY-ESO in synovial sarcoma (search) around year-end 2016. The company is also exploring the therapy's potential in myxoid round cell liposarcoma (search), myeloma, melanoma (search), ovarian cancer (search), and non-small cell lung cancer (search).
Synovial Sarcoma and Unmet Need
Synovial sarcoma (search) is a type of soft tissue sarcoma, a cancer that develops from soft tissues like fat, muscle, nerves, fibrous tissues, blood vessels, or deep skin tissues. Surgical resection is the standard therapy for localized disease, often supplemented with radiation therapy. Despite these treatments, there remains a significant unmet need for effective therapies, particularly for patients with metastatic or recurrent disease. The American Cancer Society estimated 11,930 new soft tissue sarcoma diagnoses in the United States in 2015, with approximately 4,870 deaths.