Bayesian Design for Identifying Cohort-Specific Optimal Dose Combinations Based on Multiple Endpoints: Application to a Phase I Trial in Non-Small Cell Lung Cancer.
Bayesian Design for Identifying Cohort-Specific Optimal Dose Combinations Based on Multiple Endpoints: Application to a Phase I Trial in Non-Small Cell Lung Cancer.
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DOI：
10.3390/ijerph182111452
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发表时间：
2021-10-30
影响因子：
--
通讯作者：
Gentzler RD
中科院分区：
文献类型：
--
作者：
Horton BJ;Wages NA;Gentzler RD
免疫疗法和化疗组合已被证明是多种情况下安全有效的治疗方法。然而，目前尚不清楚为达到最大耐受剂量而开发的批准剂量的化疗是否是将细胞毒性化疗与免疫疗法结合以诱导免疫应答的理想剂量。这项调节剂量化疗和帕博利珠单抗（有或没有第二种免疫调节剂）的试验使用贝叶斯设计，通过平衡两个队列中化疗和免疫治疗剂的安全性和疗效来选择最佳治疗组合。模拟研究提供的证据表明，拟定的贝叶斯设计成功实现了主要研究目的，即确定两个独立患者队列中每个队列的最佳剂量组合。这一结论得到了高比例模拟试验的支持，这些试验选择了安全且高效的治疗组合。拟议的试验得到了资助，并正在最后确定时，赞助公司决定不继续进行，由于在另一个患者群体的阴性结果。随着多种化疗和免疫治疗组合成为标准治疗，拟议的试验设计将继续具有相关性，未来的研究将需要评估多种药物方案中各种成分的适当剂量。
Immunotherapy and chemotherapy combinations have proven to be a safe and efficacious treatment approach in multiple settings. However, it is not clear whether approved doses of chemotherapy developed to achieve a maximum tolerated dose are the ideal dose when combining cytotoxic chemotherapy with immunotherapy to induce immune responses. This trial of a modulated dose chemotherapy and Pembrolizumab, with or without a second immunomodulatory agent, uses a Bayesian design to select the optimal treatment combination by balancing both safety and efficacy of the chemotherapy and immunotherapy agents within each of two cohorts. The simulation study provides evidence that the proposed Bayesian design successfully addresses the primary study aim to identify the optimal dose combination for each of the two independent patient cohorts. This conclusion is supported by the high percentage of simulated trials which select a treatment combination that is both safe and highly efficacious. The proposed trial was funded and was being finalized when the sponsoring company decided not to proceed due to negative findings in another patient population. The proposed trial design will continue to be relevant as multiple chemotherapy and immunotherapy combinations become the standard of care and future research will require evaluating the appropriate doses of various components of multiple drug regimens.
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I阶段试验的设计完全或部分有序的组。
影响因子：
2
作者：
Conaway MR
通讯作者：
Conaway MR
DOI：
10.1177/1740774518801599
发表时间：
2019-03
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Horton BJ;Wages NA;Conaway MR
通讯作者：
Conaway MR
DOI：
10.1177/1740774517722760
发表时间：
2017-10
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Conaway M
通讯作者：
Conaway M
DOI：
10.3390/ijerph18020530
发表时间：
2021-01-10
影响因子：
--
作者：
Giovagnoli A
通讯作者：
Giovagnoli A
影响因子：
1.9
作者：
OQUIGLEY, J;PEPE, M;FISHER, L
通讯作者：
FISHER, L