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.

Automated summary

This study investigated the exposure-response relationships of Camidanlumab Tesirine (Cami) using an integrated population pharmacokinetic model. The results showed a significant positive relationship between exposure and overall response rate/overall survival, but this effect was non-significant in the final models due to covariate effects. Higher exposures of Cami were associated with a higher probability of experiencing grade >= 2 adverse events at cycle 6.