Analysis of Phase I Clinical Trial Design of Anti-Cancer Agents

Area of Science:

• Oncology
• Clinical Pharmacology
• Drug Development

Background:

• Cancer research has evolved significantly since 2000, driven by advances in molecular biology and technology.
• This has led to the development of novel anti-cancer therapies with diverse mechanisms of action.
• Regulatory changes have also influenced the landscape of cancer drug development.

Purpose of the Study:

• To analyze trends and key features of Phase 1 clinical trial designs for U.S. FDA-approved anti-cancer agents.
• To examine the period between 2013 and 2024 for approved anti-cancer drugs and their trial designs.
• To identify common drug classes, primary indications, and trial methodologies.

Main Methods:

• Retrospective analysis of U.S. FDA-approved anti-cancer drugs from 2013-2024.
• Categorization of drugs by class, focusing on targeted therapies and bi-specific T-cell engagers.
• Review of Phase 1 clinical trial designs, including objectives, randomization, and dose escalation methods.

Main Results:

• Targeted therapies were the most frequent class (86 approvals), with a notable rise in bi-specific T-cell engagers.
• Lung cancer and leukemia had the highest number of initial indications (24 and 21, respectively).
• Phase 1 trials commonly aimed to determine Dose-Limiting Toxicity (DLT), Maximum Tolerated Dose (MTD), and Recommended Phase 2 Dose (RP2D), using non-randomized, open-label, seamless designs with the 3+3 dose escalation model.

Conclusions:

• Phase 1 trial designs for anti-cancer drugs are largely non-randomized, open-label, and utilize seamless dose expansion.
• Targeted therapies dominate approvals, with increasing interest in bi-specific T-cell engagers.
• The 3+3 dose escalation design remains the standard for early-phase anti-cancer drug trials.