1494 Abstract withdrawn
Year: 2024
Type: conference-abstract
Abstract: Background 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. Methods 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. Results 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>50%, 2/2 with TPS=1–49% and 1/1 with TPS<1%. Conclusions 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. Trial Registration ClinicalTrials.gov ID NCT05978102.
Authors: Chengying Kong, Jingnan Zhang, Li Sun, Qijia Xuan, Haining Huang, Kai Wang
Institution: Zhejiang University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4404066731