Abstract CT010: A phase I study of the oncolytic peptide LTX-315 generates de novo T-cell responses and clinical benefit in patients with advanced sarcoma

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 m