Related Experiment Video

Updated: Oct 19, 2025

A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research
08:17

A Human Peripheral Blood Mononuclear Cell PBMC Engrafted Humanized Xenograft Model for Translational Immuno-oncology I-O Research

Published on: August 15, 2019

14.8K

Healthy volunteers in first-in-human oncology drug development for small molecules

Begoña de Las Heras1,2, Dalila Bouyoucef-Cherchalli1, Lesley Reeve1

  • 1Labcorp Drug Development Inc., headquarters in Burlington, North Carolina, USA.

British Journal of Clinical Pharmacology
|September 24, 2021
PubMed

Insights

This review explores using healthy volunteers (HVs) in early oncology trials for small molecules. This approach offers early safety and pharmacokinetic data, potentially accelerating drug development for patients.

Area of Science:

  • Oncology
  • Clinical Pharmacology
  • Drug Development

Background:

  • Traditional early oncology trials primarily used cancer patients.
  • Small molecules (targeted, immunomodulatory) present new opportunities for early volunteer studies.
  • Classic chemotherapy did not anticipate using healthy volunteers in early trials.

Purpose of the Study:

  • To provide guidance on incorporating healthy volunteers (HVs) into first-in-human (FIH) oncology trials for small molecules.
  • To address the benefits and risks of using HVs in early oncology drug development.
  • To outline the necessary nonclinical data package for FIH oncology trials in HVs.

Main Methods:

  • Review of regulatory guidance and ethical considerations for HV use in oncology.
  • Analysis of nonclinical study requirements (toxicokinetics, pharmacokinetics, safety pharmacology, toxicology, genotoxicity).
  • Comparison of trial designs involving HVs versus cancer patients (CPs).

Main Results:

  • A robust nonclinical package is essential for FIH oncology trials in HVs.
  • Early characterization of pharmacokinetics and safety is possible in HVs without comorbidities.
  • This strategy avoids ethical concerns of sub-therapeutic dosing in CPs.

Conclusions:

  • Using HVs in early oncology trials with small molecules is a viable strategy.
  • Careful consideration of regulatory guidance, benefits, and risks is crucial for stakeholders.
  • This approach may accelerate clinical drug development timelines for patient benefit.
Keywords:
first-in-humanhealthy volunteersnonclinicaloncologypharmacokineticphase 1safetytoxicity

More Related Videos

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.3K
Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis07:40

Preparation of Peripheral Blood Mononuclear Cell Pellets and Plasma from a Single Blood Draw at Clinical Trial Sites for Biomarker Analysis

Published on: March 20, 2021

17.4K

Related Concept Videos

Bioavailability Study Design: Healthy Subjects Versus Patients01:15

Bioavailability Study Design: Healthy Subjects Versus Patients

Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
25
Preclinical Development: Overview01:28

Preclinical Development: Overview

Preclinical development consists of a series of tests that ensure the safety and efficacy of a new therapeutic compound before it is tested in humans. There are four main phases to this process. First, safety pharmacology tests are conducted to ensure the drug does not produce any acutely harmful effects. These tests examine parameters such as bronchoconstriction, cardiac dysrhythmias, blood pressure changes, and ataxia. Next, preliminary toxicological testing is performed to determine the...
5.3K
Clinical Trials: Overview01:11

Clinical Trials: Overview

Clinical development focuses on how the drug will interact with the human body and encompasses four key phases of clinical trials, each serving a specific purpose in assessing the safety and effectiveness of new drugs. These phases overlap and build upon one another. Phase I involves a small group of healthy volunteers (typically 20-80 individuals) or, in cases where significant toxicity is expected, patients with the targeted disease, such as cancer or AIDS. The volunteers are tested for...
3.9K
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
9.6K
In Vitro Drug Release Testing: Overview, Development and Validation01:10

In Vitro Drug Release Testing: Overview, Development and Validation

In vitro dissolution and drug release tests assess how quickly and how much of a drug is released from its dosage form into an aqueous medium under standardized laboratory conditions. These tests are essential tools in pharmaceutical development and quality assurance, offering insight into the drug's performance before clinical use.During formulation development, dissolution testing identifies incomplete or inconsistent drug release issues. It also supports decisions on selecting the optimal...
44
Bioequivalence studies: Biowaivers01:13

Bioequivalence studies: Biowaivers

Body:In certain scenarios, in vitro dissolution tests can replace in vivo bioequivalence studies. This is particularly true when a drug product, though available in varying strengths, maintains proportional similarity in its active and inactive ingredients. In such cases, the need for in vivo bioequivalence studies for lower strength variants may be waived, provided dissolution tests and in vivo studies on the highest strength yield satisfactory results.Bioequivalence can be indicated through...
27