Cancer Immunotherapy: Factors Important for the Evaluation of Safety in Nonclinical Studies

Area of Science:

• Oncology
• Immunology
• Pharmacology

Background:

• Immunotherapies targeting the immune system, not tumors, have transformed cancer treatment.
• The success of these therapies drives research into new targets and combination strategies.
• While beneficial, immunotherapies can cause toxicity due to exaggerated immune activation.

Purpose of the Study:

• To review the unique challenges in nonclinical safety assessment of monoclonal antibodies targeting immune checkpoint inhibitors and costimulatory molecules.
• To discuss the predictivity of animal models for safety assessment and first-in-human dose setting.
• To explore novel approaches for addressing safety issues in immuno-oncology drug development.

Main Methods:

• Review of existing literature and clinical development experience with immuno-oncology monoclonal antibodies.
• Analysis of challenges in translating nonclinical in vitro and in vivo data to human findings.
• Discussion of factors and novel approaches for safety assessment.

Main Results:

• Significant experience has been gained with approved and investigational immuno-oncology monoclonal antibodies.
• Challenges exist in predicting safety and translatability of nonclinical data to humans.
• The development of these drugs highlights the need for improved safety assessment strategies.

Conclusions:

• Nonclinical safety assessment of immuno-oncology drugs presents unique challenges.
• Improved predictive models and translatability are crucial for safe and effective drug development.
• Addressing safety issues is paramount for advancing immuno-oncology therapies.