2024 World Conference on Lung Cancer (WCLC) - Posters-P4.11E.28 Pharmacological Comparison of Dostarlimab and Pembrolizumab in Metastatic Non-Small Cell Lung Cancer in PERLA

P4.11E.28 Pharmacological Comparison of Dostarlimab and Pembrolizumab in Metastatic Non-Small Cell Lung Cancer in PERLA

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The study presented at the 2024 World Conference on Lung Cancer by Tanay Samant and colleagues compares the pharmacological effects of dostarlimab and pembrolizumab as first-line treatments for metastatic non-small cell lung cancer (NSCLC) within the PERLA trial. This double-blind study aims to comprehensively assess these agents, both of which are PD-1 inhibitors, to understand differences in overall survival (OS), overall response rate (ORR), pharmacokinetics (PK), functional receptor occupancy (fRO), and tumor dynamics.<br /><br />Key findings from the research indicate no significant PK variations between the PERLA and historical data for either drug, and similar fRO measures. However, dostarlimab showed a numerically favorable OS and ORR compared to pembrolizumab. The distinct binding mode of dostarlimab might contribute to its observed trend towards a more substantial and lasting tumor response, as suggested by the tumor size–overall survival (TS-OS) model.<br /><br />The study reported a median OS of 19.4 months for dostarlimab, compared to 15.9 months for pembrolizumab. The RECIPE v1.1 confirmed an ORR of 45% for dostarlimab and 39% for pembrolizumab. Both therapies displayed similar safety profiles, consistent with previous studies on PD-1 inhibitors.<br /><br />Binding assessments revealed that dostarlimab has a unique binding mode distinct from pembrolizumab, possibly leading to a more potent inhibition of PD-1/PD-L1 interactions. The distinct epitope and paratope of dostarlimab result in a greater steric clash with PD-L1, which might explain the deeper tumor responses observed with dostarlimab in the study.<br /><br />Overall, the study underscores the necessity for further investigation into the clinical implications of dostarlimab's distinct binding properties, which might offer insights for optimizing therapeutic strategies in NSCLC treatment.

Asset Subtitle

Tanay Samant

Meta Tag

Speaker Tanay Samant

Topic Metastatic NSCLC – Immunotherapy

Keywords

dostarlimab

pembrolizumab

NSCLC

PD-1 inhibitors

PERLA trial

overall survival

overall response rate

pharmacokinetics

tumor dynamics

binding mode