An Integrated Analysis of Dostarlimab Immunogenicity.

Area of Science:

• Immunology
• Oncology
• Pharmacology

Background:

• Monoclonal antibodies targeting programmed cell death 1 (PD-1) and its ligand (PD-L1) have transformed cancer immunotherapy.
• Development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) can challenge the efficacy and safety of these immunotherapies.

Purpose of the Study:

• To analyze the immunogenicity of dostarlimab (TSR-042), a humanized anti-PD-1 antibody, in patients with solid tumors.
• To assess the incidence of treatment-emergent antibodies and their impact on efficacy and safety.

Main Methods:

• Analysis of immunogenicity data from the GARNET trial, a phase 1 study of dostarlimab monotherapy.
• Evaluation of antibody prevalence and treatment-emergent antibodies in a large patient cohort (n=478).

Main Results:

• A low incidence of treatment-emergent antidrug antibodies (ADAs) was observed (2.5%) at the recommended dose.
• Neutralizing antibodies (NAbs) were detected in a small percentage of patients (1.3%).
• No significant impact on dostarlimab efficacy or safety was noted in patients who developed ADAs.

Conclusions:

• Dostarlimab treatment is associated with a low risk of clinically meaningful immunogenic responses.
• The observed immunogenicity profile supports the established safety and efficacy of dostarlimab in cancer patients.