Abstract 6573: Drug Combo: A unique resource for efficient phase 1 trial design with manually curated MTD and DLT

Abstract Background: With prior preclinical and clinical knowledge, an effective and efficient cancer drug combinatory trial design could be expected, which will significantly accelerate the translation. However, our internal survey results suggested that some knowledge and data sources were underused or underestimated by researchers. One primary reason is that knowledge of drug combinations is scattered in many distinct databases. Moreover, some essential information, such as MTD and DLT was missed in current databases. Drug Combo (https://drugcombo.shinyapps.io/DrugCombo/) is the first knowledge base that integrates drug toxicity and PK data that may help design an efficient Phase I trial. It is a unique informatics resource that manually curated MTD and DLT are well organized in the knowledgebase. Methods: Drug Combo integrates various publicly available PK and toxicity knowledge for individual drugs and drug combinations (Table 1). More importantly, it is the unique knowledgebase with MTD and DLT. An expert team manually curated MTD and DLT data from publicly available publications. Some standard healthcare terminologies, e.g., Rx-Norm and MedDRA were applied for concept normalization at the back end. We implemented a User-Centered Design process in the user interface (UI).The UI layout will be simple, consistent, purposeful, comprehensive, easy to navigate and informative with readable or scannable typography. A summary view was provided to inform users of some essential information, e.g., MTD, and Overlapping toxicities. The user can find the details in the “Detail Tab”. Results: Currently, Drug Combo integrates pharmacological, pharmacokinetics, and toxicity data. Especially, MTD and DLT data from more than 1,600 published Phase I trials results are exclusive in Drug Combo. Conclusions: Drug Combo is the first knowledge base that provides expert-curated MTD and DLT information. It could help design an effective and efficient drug combination phase 1 trial. Current knowledge type in Drug Combo Type Source Drug Names DrugBank, RxNorm Target DrugBank, Manual curation Associated Condition RxNorm, Drug Labels PK profiles DrugBank Adverse Drug Event Drug Label, FAERS MTD Manual curation DLT Manual curation DDI DrugBank, Manual curation Citation Format: Lei Wang, Shijun Zhang, Lai Wei, Yuxi Zhu, Dwight Owen, Lang Li. Drug Combo: A unique resource for efficient phase 1 trial design with manually curated MTD and DLT [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6573.