CRM and partial order CRM with adaptive rescaling for dose‐finding in immunotherapy trials with a continuous outcome

In many phase 1 oncology trials of immunotherapies, no dose‐limiting toxicities are observed and the maximum tolerated dose cannot be identified. In these settings, dose‐finding can be guided by a biomarker of response rather than the occurrences of dose‐limiting toxicity. The recommended phase 2 do...

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Bibliographic Details
Published inStatistics in medicine Vol. 42; no. 14; pp. 2409 - 2419
Main Authors Saha, Pooja T., Fine, Jason P., Ivanova, Anastasia
Format Journal Article
LanguageEnglish
Published Hoboken, USA John Wiley & Sons, Inc 30.06.2023
Wiley Subscription Services, Inc
Subjects
Biomarkers
Computer Simulation
continual reassessment method
Dose-Response Relationship, Drug
Humans
Immunotherapy
Maximum Tolerated Dose
Medical Oncology
Neoplasms - drug therapy
partial order
phase 1 clinical trials
quasi‐likelihood
Research Design
continual reassessment method
phase 1 clinical trials
partial order
quasi-likelihood
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Summary:In many phase 1 oncology trials of immunotherapies, no dose‐limiting toxicities are observed and the maximum tolerated dose cannot be identified. In these settings, dose‐finding can be guided by a biomarker of response rather than the occurrences of dose‐limiting toxicity. The recommended phase 2 dose can be defined as the dose with mean response equal to a prespecified value of a continuous response biomarker. To target the mean of a continuous biomarker, we build on the idea of the continual reassessment method and the quasi‐Bernoulli likelihood. We extend the design to a problem of finding the recommended phase 2 dose combination in a trial with multiple immunotherapies.
Bibliography:ObjectType-Article-1
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ISSN:0277-6715
1097-0258
DOI:10.1002/sim.9729