Application of quantitative pharmacology analysis to support early clinical development of oncology drugs: dose selection.

IF 1.3 4区医学 Q4 PHARMACOLOGY & PHARMACY

Xenobiotica Pub Date : 2024-07-01 Epub Date: 2024-08-21 DOI:10.1080/00498254.2024.2377577

Ningyuan Zhang, Yu Li, Wenbin Cui, Xiangqing Yu, Ying Huang

{"title":"Application of quantitative pharmacology analysis to support early clinical development of oncology drugs: dose selection.","authors":"Ningyuan Zhang, Yu Li, Wenbin Cui, Xiangqing Yu, Ying Huang","doi":"10.1080/00498254.2024.2377577","DOIUrl":null,"url":null,"abstract":"<p><p>The selection of appropriate starting dose and suitable method to predict an efficacious dose for novel oncology drug in the early clinical development stage poses significant challenges. The traditional methods of using body surface area transformation from toxicology studies to predict the first-in human (FIH) starting dose, or simply selecting the maximum tolerated dose (MTD) or maximum administered dose (MAD) as efficacious dose or recommended phase 2 dose (RP2D), are usually inadequate and risky for novel oncology drugs.Due to the regulatory efforts aimed at improving dose optimisation in oncology drug development, clinical dose selection is now shifting away from these traditional methods towards a comprehensive benefit/risk assessment-based approach. Quantitative pharmacology analysis (QPA) plays a crucial role in this new paradigm. This mini-review summarises the use of QPA in selecting the starting dose for oncology FIH studies and potential efficacious doses for expansion or phase 2 trials. QPA allows for a more rational and scientifically based approach to dose selection by integrating information across studies and development phases.In conclusion, the application of QPA in oncology drug development has the potential to significantly enhance the success rates of clinical trials and ultimately support clinical decision-making, particularly in dose selection.</p>","PeriodicalId":23812,"journal":{"name":"Xenobiotica","volume":" ","pages":"420-423"},"PeriodicalIF":1.3000,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Xenobiotica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00498254.2024.2377577","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/21 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 0

Abstract

The selection of appropriate starting dose and suitable method to predict an efficacious dose for novel oncology drug in the early clinical development stage poses significant challenges. The traditional methods of using body surface area transformation from toxicology studies to predict the first-in human (FIH) starting dose, or simply selecting the maximum tolerated dose (MTD) or maximum administered dose (MAD) as efficacious dose or recommended phase 2 dose (RP2D), are usually inadequate and risky for novel oncology drugs.Due to the regulatory efforts aimed at improving dose optimisation in oncology drug development, clinical dose selection is now shifting away from these traditional methods towards a comprehensive benefit/risk assessment-based approach. Quantitative pharmacology analysis (QPA) plays a crucial role in this new paradigm. This mini-review summarises the use of QPA in selecting the starting dose for oncology FIH studies and potential efficacious doses for expansion or phase 2 trials. QPA allows for a more rational and scientifically based approach to dose selection by integrating information across studies and development phases.In conclusion, the application of QPA in oncology drug development has the potential to significantly enhance the success rates of clinical trials and ultimately support clinical decision-making, particularly in dose selection.

查看原文本刊更多论文

应用定量药理学分析支持肿瘤药物的早期临床开发：剂量选择。

在早期临床开发阶段，选择合适的起始剂量和合适的方法来预测新型肿瘤药物的有效剂量是一项重大挑战。传统的方法是利用毒理学研究中的体表面积转换来预测首次用药（FIH）的起始剂量，或者简单地选择最大耐受剂量（MTD）或最大给药剂量（MAD）作为有效剂量或第二阶段推荐剂量（RP2D），但这些方法对于新型肿瘤药物来说通常是不够的，而且存在风险。定量药理学分析（QPA）在这一新模式中发挥着至关重要的作用。本篇微型综述总结了 QPA 在选择肿瘤 FIH 研究起始剂量和扩增或 2 期试验潜在有效剂量方面的应用。总之，在肿瘤药物开发中应用 QPA 有可能显著提高临床试验的成功率，并最终支持临床决策，尤其是在剂量选择方面。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Xenobiotica 医学-毒理学

CiteScore

3.80

自引率

5.60%

发文量

审稿时长

2 months

期刊介绍： Xenobiotica covers seven main areas, including:General Xenobiochemistry, including in vitro studies concerned with the metabolism, disposition and excretion of drugs, and other xenobiotics, as well as the structure, function and regulation of associated enzymesClinical Pharmacokinetics and Metabolism, covering the pharmacokinetics and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in manAnimal Pharmacokinetics and Metabolism, covering the pharmacokinetics, and absorption, distribution, metabolism and excretion of drugs and other xenobiotics in animalsPharmacogenetics, defined as the identification and functional characterisation of polymorphic genes that encode xenobiotic metabolising enzymes and transporters that may result in altered enzymatic, cellular and clinical responses to xenobioticsMolecular Toxicology, concerning the mechanisms of toxicity and the study of toxicology of xenobiotics at the molecular levelXenobiotic Transporters, concerned with all aspects of the carrier proteins involved in the movement of xenobiotics into and out of cells, and their impact on pharmacokinetic behaviour in animals and manTopics in Xenobiochemistry, in the form of reviews and commentaries are primarily intended to be a critical analysis of the issue, wherein the author offers opinions on the relevance of data or of a particular experimental approach or methodology