Abstract 4487: CTS2190, a first-in-class PRMT1 inhibitor in phase I/II clinical development, demonstrates robust and broad monotherapy efficacy and provides a rationale for novel combinations based on translational findings.

Abstract Background: ​​ Protein arginine methyltransferase 1 (PRMT1) is a master epigenetic regulator implicated in oncogenesis through diverse mechanisms, including signal transduction, DNA damage repair, and immune evasion. CTS2190 was designed as a first-in-class, oral PRMT1 inhibitor to achieve high selectivity and minimize off-target toxicity. This agent is currently being evaluated in a phase I/II clinical trial (NCT06224387) and has shown encouraging efficacy and a favorable safety profile, with no thrombotic events observed, in heavily pretreated patients with advanced solid tumors. ​ Methods: ​​ The potency and selectivity of CTS2190 were characterized through biochemical and cellular assays. Its monotherapy efficacy was evaluated in multiple cell-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Furthermore, the combinatorial potential of CTS2190 was investigated with targeted therapies (Enzalutamide, Osimertinib, Gilteritinib), a radioligand therapy (Lu177-PSMA), and an anti-PD-1 antibody across relevant in vivo models. Tumor growth and immune profiling were assessed. ​ Results: ​​ CTS2190 exhibited high selectivity for PRMT1 and potent dose-dependent antitumor activity as a single agent in various CDX and PDX models, leading to significant tumor growth inhibition. This robust monotherapy efficacy provided a strong foundation for exploring combinations. CTS2190 demonstrated robust synergistic antitumor activity with all combination partners. It enhanced the efficacy of targeted agents, sensitized tumors to radiation, and remodeled the tumor immune microenvironment. ​ Conclusion: ​​ The compelling single-agent activity of CTS2190 in preclinical models corroborates its ongoing clinical investigation. The broad and potent synergy observed with targeted, radioligand, and immunotherapeutic agents provides a strong mechanistic rationale for the imminent clinical development of novel CTS2190-based combination regimens, positioning it as a versatile therapeutic strategy for multiple cancers. Citation Format: Hui Shi, Qiugeng Ouyang, Jiaxin Huang, Xingnian Fu, Guoliang Xu, Haiping Wu. CTS2190, a first-in-class PRMT1 inhibitor in phase I/II clinical development, demonstrates robust and broad monotherapy efficacy and provides a rationale for novel combinations based on translational findings​ abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4487.