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

Grace Omes-Smit1, Marjolein Garsen2, Alex Zwiers2

  • 1Zwiers Regulatory Consultancy, Gasstraat 20, 5349 AA, Oss, The Netherlands. Grace.Omes-Smit@az-regulatory.com.

Therapeutic Innovation & Regulatory Science
|August 11, 2021
PubMed
Abstract

Insights

Despite positive genotoxic findings, 12 anticancer drugs were safely administered to healthy volunteers (HVs) in clinical trials. Comprehensive testing confirmed no genotoxic risks at human exposure doses, demonstrating safety for HVs in cancer drug development.

Area of Science:

  • Oncology
  • Pharmacology
  • Toxicology

Background:

  • Advancements in cancer research enable the inclusion of healthy volunteers (HVs) in clinical trials for novel immunomodulatory and molecularly targeted drugs.
  • Chemotherapeutics historically posed safety concerns, limiting HV participation.

Purpose of the Study:

  • To determine the number of marketing authorization applications (MAAs) involving HVs.
  • To identify anticancer drugs administered to HVs despite positive genotoxicity findings.
  • To evaluate the dosage and justification for HV studies with genotoxic drugs.

Main Methods:

  • Analysis of European Medicines Agency (EMA) data from January 2010 to December 2019.
  • Review of European Public Assessment Reports (EPARs) for genotoxicity data and HV enrollment.
  • Identification of small molecule anticancer drugs and their associated clinical trial data.

Main Results:

  • 71 MAAs for small molecule anticancer drugs were identified.
  • 48 anticancer drugs were studied in HVs.
  • 12 anticancer drugs were administered to HVs despite positive genotoxic findings, yet extensive testing showed no cellular risk.

Conclusions:

  • Comprehensive genetic toxicology testing can demonstrate the absence of genotoxic risks in HVs, even with initial positive findings.
  • Anticancer drugs administered to HVs in this study posed no harm at the evaluated human exposure doses.
  • The inclusion of HVs in clinical trials for anticancer drugs is feasible and safe under rigorous toxicological evaluation.
Keywords:
Clinical trialsDrug developmentGenetic toxicologyGenotoxicity testingHealthy volunteersOncology

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