An Integrated Analysis of Dostarlimab Immunogenicity

Abstract

Monoclonal antibodies that block the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) have revolutionized cancer immunotherapy. However, immunogenic responses to these new therapies—such as the development of antidrug antibodies (ADAs) and neutralizing antibodies (NAbs)—may represent a significant challenge to both efficacy and safety in some patients. Dostarlimab (TSR-042) is an approved, humanized, anti-PD-1 monoclonal antibody that has shown efficacy in multiple solid tumor types. Here, we report the results of an immunogenicity analysis of dostarlimab monotherapy in patients enrolled in the GARNET trial, a multicenter, open-label, single-arm phase 1 study. Overall, 477 of 478 patients (99.8%) were included in the analysis of dostarlimab antibody prevalence, and 349 out of 478 enrolled patients (73.0%) were evaluable for treatment-emergent antibodies to dostarlimab. The incidence of treatment-emergent ADAs was 2.5% at the recommended therapeutic dose (500 mg Q3W for the first 4 doses, 1000 mg Q6W until discontinuation), which is comparable to other anti-PD-(L)1 drugs. NAbs were detected in only 1.3% of patients. In the small percentage of patients who developed ADAs, there was no evidence of altered efficacy or safety of dostarlimab at the recommended dosing regimen. These findings demonstrated that treatment with dostarlimab was associated with a low risk of eliciting clinically meaningful ADAs over the course of this study, and dostarlimab is already approved by health authorities.

The Impact of the Microbiome on Resistance to Cancer Treatment with Chemotherapeutic Agents and Immunotherapy

“…Hodi et al documented a higher clinical benefit in the group of advanced melanoma patients treated with nivolumab together with ipilimumab compared to the patients on nivolumab therapy alone [ 114 ]. More recently, the approved cemiplimab and dostarlimab are also effective antibodies targeting the PD-1 signaling pathway [ 115 ] and several other PD-1 inhibitors are currently under development [ 116 ].…”

Dostarlimab: From preclinical investigation to drug approval and future directions

“…The incidence of dostarlimab-emergent ADAs (including both the treatment-induced and the treatment-boosted ADAs) was of 2.5%, which is globally comparable to other mAbs directed against the same target; moreover, the development of ADAs did not affect significantly dostarlimab pharmacokinetics nor had an impact on safety and efficacy measures. 5 …”

Dostarlimab as a Miracle Drug: Rising Hope against Cancer Treatment

“…This assay also showed the enhanced activity of dostarlimab when TIM3 antibodies or LAG3 antibodies were present. In the presence of antibodies, dostarlimab exhibited increased activity, but no significant cytokine release was observed from human PBMCs (peripheral blood mononuclear cells) [ 29 ].…”