Abstract 2574: Q901; a highly selective covalent cdk7 inhibitor inducing substantial anti-tumor effect in a broad spectrum of solid tumor lineages

Abstract As a key regulator of its dual role in transcription and cell cycle progression, CDK7 has been determined to be an attractive therapeutic target in a variety of tumor types driven by cell cycle dysregulation and aberrant control of the transcriptional processes. Q901 is an irreversible small molecule inhibitor with extreme selectivity and potent inhibition activity for CDK7, which forms a covalent bond with C312 of the CDK7 C-terminal domain. Q901 demonstrated selective cytotoxic activities in a broad spectrum of solid tumor lineages. TP53 mutation could be a potential predictive marker for the Q901 response as TP53 wild-type cancer cells demonstrates a significantly increased cytotoxic response compared to TP53 mutant cells in the bioinformatic analysis. In addition, gene expression profiling analysis showed a dose-response increase of POLR2A expression upon Q901 treatment and a correlation with tumor growth inhibition rate, indicating that POLR2A might be a potential PD marker for the Q901-induced response. Taken together, these data support the clinical development of Q901 for solid tumor indications. Q901 is progressing to IND-enabling studies to support the start of Phase 1 oncology clinical trials in early 2022. Citation Format: Donghoon Yu, Yeejin Jeon, Seung-Joo Lee, Jaeseung Kim, Kiyean Nam. Q901; a highly selective covalent cdk7 inhibitor inducing substantial anti-tumor effect in a broad spectrum of solid tumor lineages [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2574.