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. 2022 Jan;56(1):76-84.
doi: 10.1007/s43441-021-00330-8. Epub 2021 Aug 11.

Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings

Grace Omes-Smit  1 , Marjolein Garsen  2 , Alex Zwiers  2
Affiliations

Healthy Volunteer Studies in the Development of Anticancer Drugs with Genotoxic Findings

Grace Omes-Smit et al. Ther Innov Regul Sci. 2022 Jan.

Abstract

Background: Recent scientific advances in cancer research have led to the development of immunomodulatory and molecularly targeted drugs with better safety profiles than chemotherapeutics, which makes it possible to include healthy volunteers (HVs) in clinical trials. In this study, we aimed to identify the number of marketing authorization applications (MAAs) that enrolled HVs in a clinical trial and to identify the number of anticancer drugs that were given to HVs despite a positive genotoxic finding. In addition, we evaluated the dose of anticancer drugs administered to HVs and the justification for proceeding with HV studies despite a positive genotoxic finding.

Methods: Publicly available information from the European Medicines Agency (EMA) website was used for this study. Anticancer drugs were identified using the human medicines highlights published by EMA between January 2010 and December 2019. EPARs were used to collect general information of the anticancer drugs, details on genotoxicity studies, and the enrollment of HVs in clinical trials.

Results: We identified 71 MAAs for small molecule anticancer drugs with a positive or negative CHMP opinion in the EU. Forty-eight anticancer drugs were studied in HVs, of which 12 anticancer drugs were administered to HVs despite positive genotoxic findings in the standard battery. Systematic and extensive genetic toxicology screening demonstrated the absence of genotoxic risks to the cell system.

Conclusion: We showed that despite a positive genotoxic finding, comprehensive genetic toxicology testing demonstrated the absence of risks to the cell system at the human exposure dose. Therefore, these anticancer drugs posed no harm to HVs.

Keywords: Clinical trials; Drug development; Genetic toxicology; Genotoxicity testing; Healthy volunteers; Oncology.

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Conflict of interest statement

The authors declare no conflicts of interest.

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