Abstract 7167: Impact of patient specific factors on exposures of tarlatamab, a half-life extended DLL3-directed bispecific T-cell engager in patients with advanced small cell lung cancer

Abstract

Abstract Background: Tarlatamab is a first in class, half-life extended delta-like ligand (DLL3) targeted bispecific T-cell engager (BiTE) immunotherapy that has shown antitumor activity with durable objective responses and promising survival outcomes in the ongoing studies in patients with previously treated small-cell lung cancer (NCT03319940, NCT05060016) (Ahn et al, 2023; Paz-Ares et al, 2023). Here we describe the effects of patient specific factors [age, sex, bodyweight, ethnicity, estimates of renal and hepatic function, prior lines of therapy, baseline disease status, emergence of anti-drug antibodies (ADA)] on tarlatamab exposures. Methods: Tarlatamab serum concentrations were available from 420 subjects (8509 samples) pooled across the ongoing Phase 1 DeLLphi-300 study (dose range 0.003 mg to 100 mg Q2W and 200 mg Q3W) and Phase 2 DeLLphi-301 study (10 mg and 100 mg Q2W). The data were analyzed using a nonlinear-mixed effects modeling approach implemented in NONMEM (v7.5) software. Model selection and evaluation was guided by standard statistical and graphical approaches. Impact of key baseline demographic variables on tarlatamab clearance and volume of distribution were evaluated. Results: Tarlatamab exposures increased in a dose-proportional manner and were not impacted by age, sex, ethnicity, estimates of renal and hepatic function, prior lines of therapy or baseline disease status. Asian race resulted in 14% higher peak serum concentrations relative to Caucasian subjects. Higher body weight (99 kg; 90th percentile) was associated with a 24% decrease in Day 28 pre-dose concentration (Ctrough) relative to median bodyweight (73 kg). Lower body weight (54 kg; 10th percentile) was associated with a 27% increase in Ctrough relative to median bodyweight. Positive ADA status resulted in a 24% decrease in Ctrough. However, at the recommended dose of 10 mg Q2W, neither body weight nor ADA status had a clinically relevant impact on tarlatamab efficacy or safety measures (Ahn et al, 2023). Conclusion: Overall, based on these analyses, no dose adjustment for tarlatamab is required based on age, sex, bodyweight, ethnicity, estimates of renal and hepatic function, prior lines of therapy, baseline disease status or emergence of ADA. Citation Format: Stephanie M. Kong, Mukul Minocha, Po-Wei Chen, Pablo Martinez, Erik S. Anderson, Amanda Parkes, Brett E. Houk, Chih-Wei Lin. Impact of patient specific factors on exposures of tarlatamab, a half-life extended DLL3-directed bispecific T-cell engager in patients with advanced small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7167.