Abstract CT137: ENLIGHTen-01: a phase 1 study of fluorescein-specific (FITC-E2)-car T cells in combination with folate-fluorescein (UB-TT170) for osteosarcoma

Abstract Background: Outcomes for relapsed osteosarcoma (OS) remain poor and there are no systemic therapies that have been shown to provide a survival benefit. Chimeric Antigen Receptor (CAR) T cell immunotherapy involves the adoptive transfer of T-lymphocytes that have been engineered to recognize tumor-specific antigens, resulting in targeted lysis of malignant cells. Folate receptors (FR) are membrane-bound surface proteins that bind folates with high affinity. FRs are overexpressed in OS and have very limited expression in normal tissue. UB-TT170 (Umoja Biopharma) is a small molecule bispecific “adapter” consisting of folate conjugated to fluorescein (FL). It penetrates tumors in minutes and is retained for long periods of time due to high affinity for the FR, while unbound UB-TT170 rapidly clears from the blood and from FR- tissues. We hypothesize that administration of fixed dosing anti-FL(FITC-E2) CAR T cells followed by escalating doses of UB-TT170 will deliver personalized immunotherapy to OS patients. In addition, this approach offers an attractive safety mechanism since administration of NaFL should reverse CAR T cell reactivity. Methods: We designed a Phase I study for young adult (15-30 yr) patients with recurrent/refractory OS to examine the safety and feasibility of administering autologous, peripheral blood-derived T cells that have been genetically modified to express a 2nd generation FL-specific CAR in combination with intra-subject dose escalation of UB-TT170. The primary objective is to identify a recommended dose escalation sequence of UB-TT170 to move forward in clinical development. A 3+3 design will be used to investigate 3 possible dosing sequences. The trial opened in July 2022. As of January 5, 2023, 5 subjects have enrolled and one subject has been treated on dose regimen 1. T cell products have been successfully manufactured for all enrolled subjects. The trial remains open to enrollment. Clinical trial registration numbers: NCT05312411 Citation Format: Catherine M. Albert, Navin R. Pinto, Mallory Taylor, Ashley Wilson, Stephanie Rawlings-Rhea, Prabha Narayanaswamy, Wenjun Huang, Kristy Seidel, Stephanie Mgebroff, Christopher Brown, Jacob Garcia, Jeffrey Teoh, Rimas J. Orentas, Rebecca A. Gardner, Michael C. Jensen, Julie R. Park. ENLIGHTen-01: a phase 1 study of fluorescein-specific (FITC-E2)-car T cells in combination with folate-fluorescein (UB-TT170) for osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT137.