Exposure–response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma
Cancer chemotherapy and pharmacology(2022)
摘要
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.
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关键词
ADCT-301,Antibody-drug conjugate,Camidanlumab tesirine,PBD,Phase 1,Predictor
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