Exposure–response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma

Purpose To investigate camidanlumab tesirine (Cami) exposure–response (E–R) relationships, using an integrated population pharmacokinetic model, for patients with classical Hodgkin lymphoma (cHL) and non-Hodgkin lymphoma enrolled in an open-label, phase 1 study (NCT02432235). Methods Exploratory analyses investigated relationships between exposure measures (C maxss , C minss , and C avgss ) and the occurrence of binary variables (overall response rate [ORR] and selected adverse events [AEs]) and nonbinary variables (overall survival [OS]). Results Exploratory analyses showed a significant, positive relationship between exposure and ORR/OS. The final model showed this effect was non-significant due to the covariate effects. Cami exposures were higher in patients with selected grade ≥ 2 AEs at cycle 6 (the anticipated steady-state exposure level), confirmed in the final E–R models. Conclusions Based on univariate results, C maxss was used as the exposure measure in all models, except for the autoimmune AE full E–R model in which C avgss was used. The positive relationship between exposure and ORR/OS (higher exposure significantly associated with higher probabilities of ORR/OS) was not statistically significant in the final models. The final safety E–R models demonstrated a significant positive association between Cami exposure and selected grade ≥ 2 AEs, with higher exposures associated with higher probabilities of experiencing the grade ≥ 2 AEs at cycle 6. The results identify preliminary predictors of efficacy and safety and provide a basis for a dosing rationale and benefit–risk profile of Cami in patients with relapsed/refractory cHL.