Synovial sarcoma recurrent

The purpose of this study is to evaluate safety and pharmacokinetics as well as the biodistribution of OTSA101-DTPA-111In and to evaluate the safety of intravenous administration of OTSA101-DTPA-90Y.

Adoptive T-cell therapy is a therapeutic approach that aims to generate an anti-tumor T-cell immune response by infusing a cancer subjects own T-cells obtained by leukapheresis, engineered and expanded in-vitro to express a tumor specific T-cell receptor. NY-ESO-1 and LAGE-1a antigens are tumor-associated proteins that have been found in several tumor types, including synovial sarcoma. This is an open-label study to evaluate the safety and efficacy of GSK3377794 (genetically engineered NY-ESO-1 Specific [c259] T Cells), in combination with anticancer agents including pembrolizumab in subjects with NY-ESO-1 and/or LAGE-1a positive relapsed and refractory synovial sarcoma. The study will consist of a target expression screening to determine if subjects are human leukocyte antigen (HLA)-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive and if their tumors express NY-ESO-1 and/or LAGE-1a, followed by a leukapheresis screening phase of up to 42 days prior to leukapheresis. Eligible subjects will enter a leukapheresis phase followed by lymphodepletion phase with cyclophosphamide and fludarabine. During the treatment phase, subjects will be administered GSK3377794 on Day 1 followed by pembrolizumab infusion once every 3 weeks from Day 22 (or Week 7) for up to 2 years. There will be a long-term follow-up phase from the end of treatment phase and for up to 15 years from the date of GSK3377794 administration.

This phase I trial studies how well autologous NY-ESO-1-specific CD8-positive T lymphocytes (modified T lymphocytes [T cells]), chemotherapy, and aldesleukin with or without dendritic cell-targeting lentiviral vector ID-LV305 (LV305) and immunotherapeutic combination product CMB305 (CMB305) work in treating participants with sarcoma that has spread to other places in the body (advanced) or that has come back (recurrent). Modified T cells used in this study are taken from participants, are changed in a laboratory, and may "kill" some types of tumor cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Cyclophosphamide may help the body get ready to receive the modified T cells. Interleukins, such as aldesleukin, are proteins made by white blood cells and other cells in the body and may help regulate immune response. LV305 and CMB305 may help stimulate the immune system. Giving modified T cells, chemotherapy, aldesleukin, LV305, and CMB305 may work better in treating participants with sarcoma.