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

Abstract

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.

Keywords: ADCT-301; Antibody-drug conjugate; Camidanlumab tesirine; PBD; Phase 1; Predictor.