|The following article features coverage from the American Society of Clinical Oncology 2020 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
A phase 2 clinical trial called IGNYTE-ESO is under way to evaluate the safety and activity of GSK3377794, an investigational autologous T-cell product, in patients with human leukocyte antigen (HLA)-A*02–positive solid tumors, including those with advanced metastatic or unresectable synovial sarcoma (ClinicalTrials.gov Identifier: NCT03967223). The trial details were reported at ASCO20 Virtual Scientific Program.
The investigational product has a T-cell receptor (TCR) for New York esophageal antigen-1 (NY-ESO-1), which is expressed in several solid tumors, especially synovial sarcoma.
“Unlike CAR T cells, TCR T cells can recognize the antigens derived from intranuclear proteins such as NY-ESO-1, which are presented as peptides in the cell surface and complexed with HLA,” said the lead author of the poster, Sandra P. D’Angelo, MD, medical oncologist at Memorial Sloan Kettering Cancer Center in New York City.
The trial includes several substudies to allow investigators to evaluate NY-ESO-1–specific T cells in multiple tumor types. Two of the substudies are for patients with advanced metastatic or unresectable synovial sarcoma whose tumors are positive for NY-ESO-1. Substudy 1 will evaluate the NY-ESO-1–specific T cells in patients with treatment-naive disease, and substudy 2 in patients whose disease progressed after anthracycline-based chemotherapy. For both substudies, all patients must have at least 1 of the following alleles: HLA-A*02:01, HLA-A*02:05, or HLA-A*02:06.
The trial began enrolling patients in December 2019, with a target enrollment of 10 patients for the treatment-naive substudy and 55 for the previously treated substudy. All patients will receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide followed by infusion with autologous NY-ESO-1–specific T cells. As part of a separate study protocol, patients may be followed for up to 15 years after infusion.
Eligibility criteria for both substudies include the patient being at least 10 years of age, having adequate organ function, having an Eastern Cooperative Oncology Group performance status of 0 or 1, and having measurable disease. Patients with central nervous system metastases are not eligible for enrollment.
Overall response rate is the primary endpoint for both substudies. There are also several secondary endpoints, which include time to response, duration of response, disease control rate, progression-free survival, and adverse events. For the previously treated substudy, overall survival and presence of antibodies to the NY-ESO-1–specific T cells will be assessed.
Read more of Cancer Therapy Advisor‘s coverage of the ASCO 2021 meeting by visiting the conference page.
D’Angelo SP, Blay J, Chow WA, et al. Safety and activity of autologous T cells with enhanced NY-ESO-1–specific T-cell receptor (GSK3377794) in HLA-a*02+ previously-treated and -untreated patients with advanced metastatic/unresectable synovial sarcoma: A master protocol study design (IGNYTE-ESO). Presented at: ASCO20 Virtual Scientific Program. J Clin Oncol. 2020;38(suppl):abstr TPS11571.