Abstract CT010: A phase I study of the oncolytic peptide LTX-315 generatesde novoT-cell responses and clinical benefit in patients with advanced sarcoma
Authors: Baaurain Jean-Francois , Jungels Christiane , Kristeleit Rebecca S. , Jossang Dag E. , Jebsen Nina L. , Rekdal Øystein , Sveinbjornsson Baldur , Gjerstad Vibeke S. , Brunsvig Paal , Galon Jerome , Hermitte Fabienne , Patel Hamina 
Published: August 2019

Abstract
Background: LTX-315 is a first-in class oncolytic peptide that has the ability to kill cancer cells and induce specific anticancer immune response when injected locally into experimental tumors established in immunocompetent mice. The underlying mechanism of action include induction of immunogenic cell death with subsequent infiltration of T-cells into the tumor microenvironment. A multicenter Phase I study was conducted to evaluate the safety and tolerability of LTX-315 in patients with solid tumors who had exhausted standard treatment options.
Methods: The primary objective of the trial was to assess the safety and tolerability of multiple, intratumoral doses of LTX-315 as a monotherapy. The secondary objective was to evaluate clinical activity (assessed using immune-related response criteria (irRC)) and the ability of LTX-315 to evoke local and systemic immune responses. Paired pre and post treatment tumor samples were obtained throughout the study. Immunohistochemistry and gene expression analysis were performed on these paired tumor biopsies. T-cell receptor (TCR) repertoire in peripheral blood and tumor biopsies was assessed by TCRβ-gene sequencing.
Results: Twenty-seven patients were treated with LTX-315 monotherapy and had at least one post baseline efficacy assessment, of which 5 patients had the diagnosis of sarcoma. Best overall response seen in the sarcoma patients was SD in 4 out of 5 patients (80%). In one patient, a marked tumor regression was observed in two distant non-injected lesions (39% and 66% reduction). All patients experienced a treatment emergent adverse event (TEAE) and all patients experienced at least one episode of LTX-315 related adverse event, most commonly an acute reaction to injection of LTX-315 such as hypotension, rash, flushing or itching. The majority (94%) of these injection-related events were grade 1. There were 2 episodes (6%) of grade 3 AE, no serious adverse events were reported. Enhanced tumor infiltration of CD3+ and CD8+T cells, assessed by immunoscore®, was observed in 100% and 75% of the responding sarcoma patients, respectively. Gene expression profiling by Immunosign ®21 in one injected lesion showed a distinct “cold to hot’’ signature change.TCR sequencing of the patient`s T cells in peripheral blood revealed significant clonal expansion of T-cells, 39% of these T cell clones were also detected in post-treatment biopsied tumors.
Conclusions: Intratumoral LTX-315 is generally safe and tolerable. LTX-315 monotherapy enhances TIL population and induces polyclonal T-cell responses Based on the data from the Phase I study, the dosing regimen of LTX-315 will be assessed and optimized to position LTX-315 as a therapeutic agent in combination with other targeted immune therapies such as checkpoint inhibitors to address an unmet need in a select group of indications. Registration number; NCT01986426
Citation Format: Jean-Francois Baaurain, Christiane Jungels, Rebecca S. Kristeleit, Dag E. Jossang, Nina L. Jebsen, Øystein Rekdal, Baldur Sveinbjornsson, Vibeke S. Gjerstad, Paal Brunsvig, Jerome Galon, Fabienne Hermitte, Hamina Patel. A phase I study of the oncolytic peptide LTX-315 generatesde novoT-cell responses and clinical benefit in patients with advanced sarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT010.