PII-063 - PHARMACOKINETICS OF TARLATAMAB, A DELTA LIKE LIGAND-3 (DLL3) TARGETED HALF-LIFE EXTENDED BISPECIFIC T-CELL ENGAGER (BITE) IMMUNOTHERAPY IN ADULT PATIENTS WITH PREVIOUSLY TREATED SMALL CELL LUNG CANCER (SCLC)

M. Minocha¹, C. Thompson¹, A. Murphy¹, Y. Zhou², A. Parkes³, X. Chen³, B. Yu³, P. Martinez⁴, B. Houk¹; ¹Clinical Pharmacology Modeling and Simulation, Amgen, ²Clinical Immunology, Amgen, ³Early Development Oncology, Amgen, ⁴Global Development Oncology, Amgen.

Background: Tarlatamab binds both DLL3 on cancer cells and cluster of differentiation-3 (CD3) on T cells leading to T cell-mediated tumor lysis. Tarlatamab has displayed manageable safety and encouraging response durability in patients with previously treated SCLC [1]. Here the pharmacokinetics from this phase 1 study are presented.

Methods: DeLLphi-300 (ClinicalTrials.gov identifier: NCT03319940) is an ongoing, international, open-label study, in previously treated adult patients with advanced SCLC [1]. Multiple escalating doses were evaluated using Q2W regimen (0.003, 0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30 and 100 mg) in a 28-day cycle. A step dose regimen was implemented to mitigate the risk of cytokine release syndrome (CRS) starting at the 3 mg dose level. The step dose employed 1 mg infusion on cycle 1 day 1 (C1D1), followed by the target dose on D8, D15 and Q2W thereafter. Other dosing regimens were explored for patient convenience or for mitigating CRS. Intensive pharmacokinetic (PK) samples were collected during the first 2 cycles, and additional samples for PK and immunogenicity were collected at regular intervals in subsequent cycles. PK data were analyzed using non-compartmental analysis and summarized. Anti-drug antibody (ADA) data its effect on PK was summarized.

Results: As of March 28, 2023, PK data were available from 202 patients (including 17 of Japanese descent). Briefly, following IV infusion, serum concentrations declined with time in a biphasic manner. Across the evaluated target dose range, the serum exposures increased in an approximately dose-proportional manner with a mean (SD) estimated terminal phase elimination half-life of 5.5 (1.6) days. Steady state was achieved by approximately C2D15. Twelve patients (12/183 evaluable; 6.6%) developed treatment-emergent ADA. Distribution of dose normalized serum concentrations were comparable between subjects who were ADA positive and those who were negative over time. In addition, distribution of exposures was comparable in Japanese subjects relative to non-Japanese subjects.

Conclusion: In patients with previously treated SCLC, tarlatamab exhibited dose proportional PK and extended half-life characteristics that support Q2W dosing interval. Japanese race and ADA did not have a clinically relevant impact on exposures.