Tarlatamab exposure-efficacy and exposure-safety relationships to inform dose selection in patients with small cell lung cancer (SCLC).

PURPOSE Tarlatamab is a first-in-class, half-life extended bispecific T-cell engager (BiTE®) immunotherapy targeting delta-like ligand 3 (DLL3) currently approved for the treatment of adult patients with small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Here we report tarlatamab exposure-response relationships to inform dose selection in patients with SCLC. EXPERIMENTAL DESIGN Pharmacokinetic data were correlated with therapeutic effect [exposure-response (ER) analyses] for efficacy and safety measures using pooled data from DeLLphi-300 and DeLLphi-301 studies. Efficacy measures included objective response rate, disease control rate, best change from baseline in tumor size, progression-free survival, and overall survival. Safety events included treatment-emergent adverse events [TEAEs], treatment-related adverse events [TRAEs], and TEAEs of interest including cytokine release syndrome [CRS], neutropenia, and neurologic toxicity including immune effector cell-associated neurotoxicity syndrome [ICANS]). Effects of patient specific factors were also assessed. Doses ranging from 0.003 mg to 100 mg Q2W and 200 mg Q3W were explored. RESULTS Significant positive ER relationships were established for all evaluated efficacy measures. Near maximal efficacy was reached at exposures associated with the clinical regimen of 10 mg Q2W. No relationships with exposure were identified for the following grade ³ 3 events: TEAEs, TRAEs, CRS, and neurologic toxicity including ICANS. A shallow trend was observed for higher percentage of patients experiencing grade ³ 3 neutropenia with higher exposures. CONCLUSIONS This analysis supports 10 mg Q2W regimen and that no dose adjustment is necessary based on age, race, bodyweight, immunogenicity, number of prior therapies or disease burden.