Based on encouraging results in the first cohort of 10 patients, presented at the American Association for Cancer Research (AACR) annual meeting in April 2015, the trial is being expanded to encompass an additional 20 patients in two further cohorts.
The expansion of Adaptimmune’s trial also triggers two milestone payments from GlaxoSmithKline (GSK). Adaptimmune is collaborating with GSK for the development of its NY-ESO TCR program through a strategic cancer immunotherapy partnership announced in June 2014. Under the terms of the agreement, GSK has an exclusive option to license Adaptimmune’s NY-ESO TCR therapeutic and upon exercise would assume full responsibility for further development and commercialization of the therapeutic.
“We are encouraged by the promising data from the first cohort of patients and pleased to have commenced enrollment into the next two cohorts of this study,” commented Dr. Rafael Amado, Adaptimmune’s Chief Medical Officer. “Metastatic synovial sarcoma is largely incurable, with as few as 20 percent of patients surviving for more than two years after diagnosis. In the first cohort of this trial, we saw evidence of antitumor activity resulting from treatment with our NY-ESO TCR therapeutic in a solid tumor setting. These early data provide confidence to expand the trial in these patients who currently lack proven, effective treatment options.”
Synovial sarcoma is a cancer of the connective tissue and a type of solid tumor primarily affecting adolescents and young adults. Most metastatic soft tissue sarcomas are currently incurable - 75 to 80 percent of patients do not survive past two to three years - and there are limited treatment options for unresectable and recurrent synovial sarcoma, which is nearly always fatal.
Adaptimmune’s clinical study includes synovial sarcoma patients who have received standard first line therapy containing ifosfamide and/or doxorubicin and who are intolerant or no longer responding to the regimen, and whose tumor expresses a tumor antigen known as NY-ESO-1. The NY-ESO-1 antigen is believed to be present in 60 to 70 percent of synovial sarcoma patients.
The primary objectives of the study are to determine the safety of adoptively transferred autologous T cells expressing an affinity enhanced T cell receptor that recognizes the NY-ESO-1 antigen in HLA-A*0201, HLA-A*0205, and/or HLA-A*0206 positive patients with unresectable, metastatic or recurrent synovial sarcoma. Secondary objectives include the determination of efficacy through response rate and duration of response.
All eligible patients will be treated with lymphodepletive chemotherapy followed by administration of Adaptimmune’s NY-ESO TCR therapeutic. In the first cohort, patients whose tumor expressed NY-ESO-1 at high levels received a single course of cyclophosphamide and fludarabine for lymphodepletion prior to administration of Adaptimmune’s NY-ESO TCR therapeutic. Cohort 2 will enroll patients whose tumor expresses lower levels of the NY-ESO-1 antigen and who will receive the same treatment as patients in the first cohort. Cohort 3 will enroll patients whose tumor expresses high levels of the NY-ESO-1 antigen and will study the removal of fludarabine as part of the lymphodepletion regimen. Both cohorts are expected to open concurrently.