1494 Abstract withdrawn

<h3>Background</h3> CTM103 is an LNP mRNA encoding an IL2Rβγ selective IL-2v derivative fused with Human Serum Album. Preclinically, the novel LNP mRNA platform allowed expression and therefore extended plasma half-life of IL2v in animal models, which is not achieved with other protein-based IL-2 drugs. CTM103 stimulated significant and sustained expansion of CD8 T cells with minimal expansion of regulatory T cells and demonstrated superior efficacy than IL-2 based drugs in multiple cancer models. Therefore, the novel design of CTM103 has the potential to fully unleash the antitumor effects of the IL-2 pathway while mitigating unwanted toxicity. <h3>Methods</h3> This first-in-human, open label phase 1 study evaluates the safety, tolerability, and initial efficacy of CTM103 with or without pembrolizumab in patients with advanced solid tumors. The design includes two portions of the study: Parts A, CTM103 monotherapy in which patients receive intravenous CTM103 once every 3 weeks (Q3W) and Part B in which patients receive CTM103 in combination with pembrolizumab (200 mg on day 1), both intravenous Q3W. Both portions consist of 3+3 escalation cohorts to define maximum tolerated dose (MTD). If response signal is observed in a given indication and dose cohort, additional 10–20 patients will be enrolled to further evaluate the safety and efficacy. <h3>Results</h3> In Part A, 9 patients in three dose cohorts received CTM103. All patients demonstrated high and prolonged plasma level of IL-2, and remarkable elevation of CD8 T cells (upto 5 folds) and NK cells (upto 25 folds). No dose-limiting toxicities (DLT) were observed. In Part B, 19 patients in two dose cohorts were enrolled, 13 of which are 1L advanced NSCLC. All patients showed increased CD8 T cells (upto 12 folds) and NK cells (upto 22 folds), and most AEs were at grade 1–2 and were mostly transient. At the cut-off date (9.9.2024), 10 of the 1L NSCLC patients reached at least one tumor evaluation time-point, 8/10 of which were evaluated to be PR (ORR=80%), including 5/7with TPS&gt;50%, 2/2 with TPS=1–49% and 1/1 with TPS&lt;1%. <h3>Conclusions</h3> CTM103 was generally well tolerated at the current dose level, which already demonstrated high and prolonged plasma level of IL-2, and robust immune stimulatory activity in promoting CD8 T cells and NK cells proliferation. Initial signs of antitumor efficacy were seen in combination with pembrolizumab, regardless of PDL-1 expression level. <h3>Trial Registration</h3> ClinicalTrials.gov ID NCT05978102.