Priorities for local immunotherapy research and drug development

Area of Science:

• Oncology
• Immunology
• Therapeutics Development

Background:

• Local immunotherapy aims to stimulate robust in situ immune responses, generating systemic antitumor immunity.
• These therapies are crucial for overcoming resistance to standard immune checkpoint inhibitors, often linked to immune suppressive tumor microenvironments.
• Direct administration into the tumor microenvironment allows local immune therapies to stimulate responses and reprogram suppressive cells.

Purpose of the Study:

• To discuss unique considerations for local immunotherapy development across the entire research and clinical trial continuum.
• To provide insights into optimizing early-phase trials for understanding biologic activity and dosing.
• To guide the selection of patient populations and treatment settings for promising local therapies.

Main Methods:

• Consensus paper based on expert discussions from a "Summit on Intralesional Immunotherapy."
• Review of strategies for early-phase trials, including pharmacodynamic endpoints and imaging.
• Discussion of optimal treatment settings, such as neoadjuvant or frontline metastatic therapy.

Main Results:

• Early phase trials should measure direct effects in the tumor microenvironment using on-treatment biopsies and imaging.
• Local immunotherapies may be best suited for neoadjuvant or frontline metastatic settings to intervene before immune suppression is fixed.
• Several classes of local immunotherapy are under investigation, including oncolytic viruses, mRNA, TLR agonists, and cytokines.

Conclusions:

• Novel local therapies show promise for expanding the field and generating systemic antitumor immunity.
• Thoughtful trial design in both early-stage and registration-intent settings is essential to accelerate advancement.
• Optimizing the development of local immunotherapies requires careful consideration of trial design, patient selection, and treatment timing.