801 PRIME™ IL-15 (RPTR-147): Preliminary clinical results and biomarker analysis from a first-in-human Phase 1 study of IL-15 loaded peripherally-derived autologous T cell therapy in solid tumor patients

Background RPTR-147 is a novel autologous non-genetically modified multi-clonal T cell product loaded with an IL15-Fc nanogel. The product was derived from rare peripherally-derived anti-tumor T cell clones that were primed against a multi-antigen cassette containing tumor associated antigens (TAA), known to be over-expressed in specific tumor types. We describe preliminary results from the ongoing first-in-human Phase 1 trial. Methods Autologous anti-TAA T cells are generated with a proprietary dendritic cell priming process and then loaded with an IL15-Fc nanogel. TAAs used in cassette: PRAME, NY-ESO-1, SSX2, Survivin and WT1. Thawed RPTR-147 is delivered by infusion. Pre- and post-treatment biopsies were collected for biomarker analysis by immunohistochemistry (IHC) and transcriptome sequencing. Serial blood collections were obtained for measuring IL-15 pharmacokinetics and pharmacodynamic parameters including plasma cytokine levels and immunophenotyping by flow cytometry. T cell receptor sequencing (TCRSeq) was used to characterize the T cell repertoire from manufactured T cell product and the patient‘s blood. Results Interim clinical and biomarker data from 17 patients with advanced metastatic disease refractory to SOC who received monthly infusions of 20-360 million cells/m², were reviewed (table 1). There were no dose-limiting toxicities and no evidence of cytokine-release syndrome. The 360M/m² dose contained 3X more IL15-Fc than the MTD of systemically administered IL15-Fc,1 but produced less than a tenth of the systemic exposure to free IL15-Fc. Currently, 360M cells/m² is considered safe and well-tolerated. Further dose escalation is planned. Matched evaluable biopsies were obtained in 7 patients. Tumor-infiltrating T cell lymphocytes was observed in 5 cases for CD8 T cells and 4 cases for CD4 T cells. A dose dependent increase in both inflammatory cytokines and NK & CD8+ T cells was observed, consistent with expected MOA and PK. TCRSeq analysis demonstrated that product specific T cell clones could be tracked in both patient‘s blood and tumor over time. Further analysis to decode the specificity of those cells and demonstrate that tumor antigen specific T cells can be found in patient‘s blood and tumor biopsies is ongoing. Of the 17 patients who received RPTR-147 infusions 10 were noted to have stable disease (SD) and in 4 patients SD lasted > 6 months. Conclusions Interim results with RPTR-147 have shown it to be well-tolerated and have a favorable safety profile. Dose-escalation is proceeding. Ongoing biomarker analysis will inform future clinical strategies in matching patients to an optimized PRIME IL-15 T cell product. Trial Registration NCT03815682 Ethics Approval The study was approved by local institutional IRBs after acceptance of the IND by the FDA. Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal. Reference Romee R, Cooley S, Berrien-Elliott MM, et al. First-in-human phase 1 clinical study of the IL-15 superagonist complex ALT-803 to treat relapse after transplantation. Blood 2018;131(23):2515-2527.