Tarlatamab Exposure-Efficacy and Exposure-Safety Relationships to Inform Dose Selection in Patients with Small Cell Lung Cancer.

[PURPOSE] Tarlatamab is a first-in-class, half-life extended bispecific T-cell engager immunotherapy targeting delta-like ligand 3, currently approved for the treatment of adult patients with small cell lung cancer with disease progression on or after platinum-based chemotherapy. In this study, we report tarlatamab exposure-response relationships to inform dose selection in patients with small cell lung cancer.

[PATIENTS AND METHODS] Pharmacokinetic data were correlated with therapeutic effect (exposure-response analyses) for efficacy and safety measures using pooled data from the 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 (TEAE), treatment-related adverse events, and TEAE of interest, including cytokine release syndrome, neutropenia, and neurologic toxicity such as immune effector cell-associated neurotoxicity syndrome. Effects of patient-specific factors were also assessed. Doses ranging from 0.003 to 100 mg every 2 weeks and 200 mg every 3 weeks were explored.

[RESULTS] Significant positive exposure-response relationships were established for all evaluated efficacy measures. Near-maximal efficacy was reached at exposures associated with the clinical regimen of 10 mg every 2 weeks. No relationships with exposure were identified for the following grade ≥3 events: TEAE, treatment-related adverse events, cytokine release syndrome, and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. A shallow trend was observed for a higher percentage of patients experiencing grade ≥3 neutropenia with higher exposures.

[CONCLUSIONS] This analysis supports a 10-mg every-2-weeks regimen and that no dose adjustment is necessary based on age, race, body weight, immunogenicity, number of prior therapies, or disease burden.