Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial
This study is an early report from a phase 1 clinical trial investigating a type of immunotherapy called T cell receptor (TCR)-engineered T cells. T cells are a type of white blood cell, and in this therapy, a patients own T cells are removed and then modified so that they attack a specific protein made by the tumor. Here the protein being targeted is called preferentially expressed antigen in melanoma (PRAME), which is found in synovial sarcoma in addition to melanoma and other solid tumors. In addition to PRAME having to be made by the tumor, the patient needs to have a specific immune HLA type (HLA-A*02). This is how the immune system recognizes foreign cells (or in this case tumor cells) compared a patient’s own cells and is different among patients.
The main purpose of this study is to determine the safety, tolerability, and maximum tolerated dose (MTD) and/or recommended dose for extension. The secondary purposes include tumor response as well as duration of response. A total of 40 patients including 8 synovial sarcoma patients were enrolled in the phase 1a dose escalation and the phase 1b dose extension groups. Overall, the treatment was determined to be safe, and the MTD was not reached. Of the 41 patients receiving treatment, severe cytokine release syndrome was observed in 2 of 41 (4.9%) patients receiving treatment, and severe neurotoxicity did not occur. An overall response rate of patients with confirmed response of 28.9% (11/38) was observed with a median duration of response of 4.4months across multiple cancers including synovial sarcoma. Overall, this early analysis showed that this therapy demonstrated acceptable safety and promising anti-tumor activity including synovial sarcoma and warrant the further studies being planned for this treatment.
Read the full study in Nature Medicine.