Adaptimmune reports data on NY-ESO SPEAR T-cell receptor therapy
Adaptimmune Therapeutics announced a presentation of updated data on its lead clinical program, an NY-ESO SPEAR T-cell receptor therapy, in patients with synovial sarcoma at the European Society for Medical Oncology 2016 Congress. The study included Cohort 1: Subjects with high NY-ESO-1 antigen expression and lymphodepletion with cyclophosphamide and fludarabine; Cohort 2: Subjects with low NY-ESO-1 antigen expression and lymphodepletion with cyclophosphamide and fludarabine; Cohort 3: Subjects with high NY-ESO-1 antigen expression and lymphodepletion with cyclophosphamide alone -- no fludarabine; and Cohort 4: Subjects with high NY-ESO-1 antigen expression and lymphodepletion with a modified lower dose than Cohort I of cyclophosphamide and fludarabine. In Cohort 1, the median duration of response is reported to be approximately 31 weeks as of the August 31 data cutoff. Ongoing NY-ESO SPEAR T-cell persistence has been observed for up to 36 months. In Cohort 2, four subjects of a targeted 10 are currently enrolled in the second cohort; three patients have been treated with NY-ESO SPEAR T-cells. As of August 31, best responses seen in these three patients were: one partial response, one stable disease, and one progressive disease. In Cohorts 3 and 4, five patients are currently enrolled in the third cohort; no objective responses have been observed to date. As pre-specified in the protocol, enrollment in cohort 3 has ceased, and company has initiated enrollment in Cohort 4. NY-ESO SPEAR T-cells continue to demonstrate a generally acceptable benefit:risk profile in all treated patients to date. Most common toxicities related to therapy can be monitored and managed with medical intervention and supportive care. While there are differences in the patient populations, incidence of cytokine release syndrome with NY-ESO-1c259 SPEAR T appears to be of lower frequency and severity than reported with CD19 CAR-T therapy. As previously reported at the 2016 Annual American Society of Clinical Oncology Meeting, there was one fatal SAE of bone marrow failure in Cohort 2 of the synovial sarcoma trial. Internal investigations have not identified a mechanism by which NY-ESO SPEAR T-cells may have caused bone marrow failure.