Related Experiment Video

Updated: Jul 5, 2025

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
08:52

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

Published on: November 22, 2021

4.0K

Adaptive phase I-II clinical trial designs identifying optimal biological doses for targeted agents and

Yong Zang1,2, Beibei Guo3, Yingjie Qiu1

  • 1Department of Biostatistics and Health Data Science, School of Medicine, Indiana University, Indianapolis, IN, USA.

Clinical Trials (London, England)
|January 11, 2024
PubMed

Insights

Innovative phase I-II clinical trial designs optimize doses for targeted cancer therapies and immunotherapies. These adaptive designs use efficacy and toxicity data to find the best biological dose, maximizing patient benefit.

Area of Science:

  • Oncology
  • Clinical Trial Design
  • Pharmacology

Background:

  • Targeted agents and immunotherapies represent a paradigm shift in cancer treatment.
  • The "more is better" principle is often inapplicable to these novel therapies due to complex mechanisms.
  • Optimizing dosage is crucial for maximizing therapeutic effects while managing toxicity.

Purpose of the Study:

  • To review innovative phase I-II clinical trial designs for targeted agents and immunotherapies.
  • To examine designs that adaptively determine patient doses based on accumulating efficacy and toxicity data.
  • To identify optimal biological doses that maximize overall therapeutic effect.

Main Methods:

  • Review of innovative phase I-II clinical trial designs, categorized into efficacy-driven, utility-based, and multi-endpoint designs.
  • Analysis of dose-outcome models, optimal biological dose definitions, dose-finding algorithms, and software implementation.
  • Illustration with two real-world phase I-II trial examples (EffTox and ISO designs).

Main Results:

  • Discussion of three main categories of adaptive phase I-II designs.
  • Presentation of dose-outcome models, dose-finding algorithms, and software tools for each design type.
  • Exemplification of design application through EffTox and ISO trials.

Conclusions:

  • Adaptive phase I-II designs are essential for optimizing novel cancer therapies.
  • These designs effectively utilize accumulated data to determine optimal biological doses.
  • A classification tree is provided to guide the selection of appropriate trial designs.
Keywords:
Bayesian adaptive designImmunotherapydose optimizationphase I–II trialtargeted agent

More Related Videos

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

16.7K
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia10:49

Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia

Published on: September 18, 2013

18.2K

Related Concept Videos

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...
3.0K
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...
4.4K
Drug Administration and Therapy Phases: Overview01:26

Drug Administration and Therapy Phases: Overview

Drugs, the chemical agents used in diagnosing, treating, or preventing diseases, undergo a four-phase process of development: pharmaceutic, pharmacokinetics, pharmacodynamics, and therapeutic.
The pharmaceutical phase focuses on leveraging the physicochemical properties of the drug to design and manufacture an effective product. Variants include orally administered tablets or capsules, topical creams or ointments, and parenteral-delivery solutions or emulsions.
The pharmacokinetic phase...
471
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...
7.9K
Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches01:23

Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches

Biopharmaceutical studies constitute a vital field aiming to enhance drug delivery methods and refine therapeutic approaches, drawing upon diverse interdisciplinary knowledge. In research methodologies, the choice between controlled and non-controlled studies significantly influences the study's reliability and accuracy.
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
129
Clinical Trials01:16

Clinical Trials

Clinical trials are prospective experimental studies conducted on humans to determine the safety and efficacy of treatments, drugs, diet methods, and medical devices. Using statistics in clinical trials enables researchers to derive reasonable and accurate conclusions from the collected data, allowing them to make wise decisions in uncertain situations. In medical research, statistical methods are crucial for preventing errors and bias.
There are four phases in a clinical trial. A phase one...
6.7K