634P - First results from phase I/II study of CTS2190, a novel small-molecule inhibitor of type I PRMTs, in patients with advanced solid tumors

Background

CTS2190 could specifically inhibit type I protein arginine methyltransferases (PRMTs) and significantly reduce intra-tumor asymmetric dimethylarginine (ADMA) level and oncogenic proliferation by epigenetic modulation, RNA splicing, DNA damage as well as remarkable cancer immune activation in various solid and/or hematological cancers. Here we report the dose escalation results from an ongoing first-in-human phase I/II study to evaluate the safety, tolerability, pharmacokinetics (PK) and efficacy of CTS2190 in patients (pts) with advanced solid tumors.

Methods

Eligible pts were enrolled in escalating dose cohorts (60 to 240 mg) administered orally until progression or unacceptable toxicity. The accelerated titration combined with Bayesian optimal interval (BOIN) design was used as the dose escalation schedule.

Results

As of Apr 2, 2024, 15 pts including 10 non-small cell lung cancer (NSCLC), 1 colorectal cancer (CRC),1 triple-negative breast cancer (TNBC), 2 head and neck squamous cell carcinoma (HNSCC) and 1 esophageal squamous cell carcinoma (ESCC) received CTS2190 treatment. Among them, 9 pts received ≥3 lines of prior therapy. Treatment-related adverse events (TRAEs) of ≥Grade 3 were platelet count decreased (33.3%), amylase increased (6.7%) and blood creatine phosphokinase increased (6.7%). Dose-limiting toxicity (DLT) was observed in 1 pt (in 240 mg) who continued treatment after dose reduction. No TRAEs led to treatment discontinuation or death. Of the 10 response-evaluable pts (>60 mg), the objective response rate (ORR) and disease control rate (DCR) were 20.0% and 70.0% respectively. In the subset of NSCLC pts, the ORR and DCR were 40.0% and 60.0% respectively. Exposure of CTS2190 increased proportionally with increasing dose. Time- and dose-dependent pharmacodynamics (PD) changes in circulating free ADMA, monomethylarginine (MMA) and symmetric dimethylarginine (SDMA) were also observed.

Conclusions

CTS2190 was well tolerated and showed encouraging antitumor activities in advanced and/or metastatic solid tumors, including NSCLC, TNBC, HNSCC and ESCC. Further investigation of CTS2190 in larger pts population is ongoing including biomarker exploration.

Clinical trial identification

NCT06224387.

Editorial acknowledgement

Legal entity responsible for the study

CytosinLab Therapeutics Co., Ltd.

Funding

CytosinLab Therapeutics Co., Ltd.

Disclosure

J. Miao, Y. Mi, S. Xing, H. Wu: Financial Interests, Personal and Institutional, Full or part-time Employment: CytosinLab Therapeutics Co., Ltd. All other authors have declared no conflicts of interest.