2024 World Conference on Lung Cancer (WCLC) - Posters-P4.11E.08 Integrated PK/PD Modeling for Uliledlimab, an Anti-CD73 Monoclonal Antibody, In Non-Small Cell Lung Cancer Patients

P4.11E.08 Integrated PK/PD Modeling for Uliledlimab, an Anti-CD73 Monoclonal Antibody, In Non-Small Cell Lung Cancer Patients

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The document focuses on the pharmacokinetic/pharmacodynamic (PK/PD) modeling and analysis of uliledlimab, an anti-CD73 monoclonal antibody, used in treating non-small cell lung cancer (NSCLC). Uliledlimab works by inhibiting CD73's enzymatic activity to reduce adenosine production, which is known to cause immunosuppression and resistance against PD-1/PD-L1 checkpoint inhibitors.<br /><br />A detailed exposure-response (E-R) analysis of uliledlimab was conducted among NSCLC patients, using data from three clinical studies. These studies analyzed uliledlimab in its monotherapy form and in combination with other therapies such as atezolizumab and toripalimab. The PK data from these studies were utilized to construct a population PK model for evaluating dosage impacts post-Phase 1 study using both nonclinical and clinical results. The studies identified that uliledlimab exposure is dose-proportional from 5 to 45 mg/kg.<br /><br />The PK/PD analysis revealed a positive relationship between uliledlimab concentration and the probability of an overall response rate (ORR) in NSCLC patients. Obtaining a trough concentration threshold of 80 μg/mL was associated with a potential progression-free survival (PFS) benefit, achieved efficiently with a 30 mg/kg dose. Most patients in the simulation achieving this threshold received this higher dosage.<br /><br />The conclusion drawn suggests that uliledlimab at a dose of 30 mg/kg, with an additional "boost" dose, could maintain required serum levels to improve the clinical response rate significantly. Ongoing research intends to optimize this combination therapy further, leveraging checkpoint inhibitors and chemotherapy.<br /><br />The findings recommended continued clinical examination of uliledlimab at optimal doses to assess its effectiveness in reducing tumor progression in NSCLC patients. A future clinical study is planned to evaluate uliledlimab's role when combined with checkpoint inhibitors and chemotherapy.

Asset Subtitle

Jaime Yanez

Meta Tag

Speaker Jaime Yanez

Topic Metastatic NSCLC – Immunotherapy

Keywords

uliledlimab

anti-CD73

monoclonal antibody

NSCLC

PK/PD modeling

exposure-response analysis

checkpoint inhibitors

dose-proportional

progression-free survival

combination therapy