Related Experiment Video
Updated: Feb 17, 2026
Identifying PD-1/PD-L1 Inhibitors with Surface Plasmon Resonance Technology
Published on: May 2, 2025
Analysis of Drug Development Paradigms for Immune Checkpoint Inhibitors
Denis L Jardim1, Débora de Melo Gagliato2, Francis J Giles3
1Department of Clinical Oncology, Hospital Sirio Libanes, Sao Paulo, Brazil. jardimde@gmail.com.
Abstract:
Immune checkpoint inhibitors have unique toxicities and response kinetics compared with cytotoxic and gene-targeted anticancer agents. We investigated the impact of innovative/accelerated immunotherapy drug development/approval models on the accuracy of safety and efficacy assessments by searching the FDA website. Initial phase I trials for each agent were reviewed and safety and efficacy data compared with that found in later trials leading to regulatory approvals of the same agents. As of June 2017, the FDA approved six checkpoint inhibitors for a variety of cancer types. All checkpoint inhibitors received a priority review status and access to at least two additional FDA special access programs, more often breakthrough therapy designation and accelerated approval. Median clinical development time (investigational new drug application to approval) was 60.77 months [avelumab had the shortest timeline (52.33 months)]. Response rates during early phase I trials (median = 16%) are higher than for phase I trials of other agents (with the exception of gene-targeted agents tested with a biomarker). Doses approved were usually not identical to doses recommended on phase I trials. Approximately 50% of types of immune-related and 43% of types of clinically relevant toxicities from later trials were identified in early-phase trials. Even so, treatment-related mortality remains exceedingly low in later studies (0.33% of patients). In conclusion, efficacy and safety of immune checkpoint inhibitors appear to be reasonably predicted from the dose-finding portion of phase I trials, indicating that the fast-track development of these agents is safe and justified. Clin Cancer Res; 24(8); 1785-94. ©2017 AACR.
Insights
Accelerated approval pathways for immune checkpoint inhibitors are safe and effective. Early phase I trials accurately predict the safety and efficacy of these novel cancer immunotherapies, justifying expedited development.
Area of Science:
- Oncology
- Immunology
- Drug Development
Background:
- Immune checkpoint inhibitors (ICIs) exhibit distinct toxicity and response patterns compared to traditional chemotherapy and gene-targeted therapies.
- Innovative drug development and approval models are increasingly utilized for novel cancer agents.
Purpose of the Study:
- To evaluate the impact of accelerated FDA approval pathways on the accuracy of safety and efficacy assessments for immune checkpoint inhibitors.
- To compare safety and efficacy data from early-phase I trials with data from later-stage trials leading to regulatory approval.
Main Methods:
- Searched the FDA website for six approved checkpoint inhibitors as of June 2017.
- Reviewed initial phase I trials for each agent, comparing safety and efficacy data with later regulatory approval data.
- Analyzed clinical development timelines, response rates in early trials, and toxicity profiles.
Main Results:
- All reviewed ICIs received priority review and utilized expedited FDA programs (e.g., breakthrough therapy, accelerated approval).
- Median development time was 60.77 months; early phase I response rates (median 16%) were higher than for other agents.
- Approximately 50% of immune-related toxicities and 43% of clinically relevant toxicities were identified in early trials, with low treatment-related mortality (0.33%).
Conclusions:
- Efficacy and safety of ICIs can be reasonably predicted from phase I dose-finding studies.
- Fast-track development of immune checkpoint inhibitors is safe and justified based on early trial data.
- Accelerated approval pathways facilitate timely patient access to promising immunotherapies.
Related Concept Videos
01:27Tumor Immunotherapy
01:28Preclinical Development: Overview
01:11Clinical Trials: Overview
01:23Types of Biopharmaceutical Studies: Controlled and Non-Controlled Approaches
Non-controlled studies, commonly employed for initial exploration, lack a control group, rendering them susceptible to biases and external influences. In contrast,...
01:26Drug Administration and Therapy Phases: Overview
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...
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...