Immune checkpoint-targeted antibodies: a room for dose and schedule optimization?

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Anti-CTLA-4 and anti-PD-1/PD-L1 are immune checkpoint inhibitors that enhance antitumor immunity.
• Their dosing was based on conventional models, with maximum tolerated dose only defined for anti-CTLA-4.
• Clinical benefit as monotherapy is limited to a subset of patients, with high costs and interpatient variability.

Purpose of the Study:

• To review the development of anti-CTLA-4 and anti-PD-1/PD-L1 immunotherapies.
• To explore optimization strategies for dosing and scheduling in clinical practice.

Main Methods:

• Literature review of existing studies on immune checkpoint inhibitors.
• Analysis of pharmacokinetic variability and clinical benefit data.
• Discussion of potential optimization options for treatment regimens.

Main Results:

• Dosing and scheduling were established using conventional drug development models.
• Significant interpatient pharmacokinetic variability exists for these monoclonal antibodies.
• Clinical benefit is observed only in a subset of patients when used as monotherapy.

Conclusions:

• Current dosing and scheduling of immune checkpoint inhibitors may not be optimal.
• Further research into optimizing dose and interval is needed for improved clinical outcomes.
• Exploration of alternative dosing strategies could enhance efficacy and reduce costs.