(S-055) Population Pharmacokinetics of Elranatamab in Chinese Patients with Relapsed or Refractory Multiple Myeloma using PRIOR Approach

Xiao-duo Guan – Clinical Pharmacology, Development China, Pfizer Inc., Beijing, China; Kai-ting Zhang – Clinical Pharmacology, Development China, Pfizer Inc., Shanghai, China; Jin-jin Zhao – Clinical Pharmacology, Development China, Pfizer Inc., Shanghai, China; Jennifer Elizabeth Hibma – Pfizer Research and Development, Pfizer Inc., La Jolla CA, USA; Mohamed Elmeliegy – Oncology Research and Development, Pfizer Inc., La Jolla CA, USA; Hua Wei – Clinical Pharmacology, Development China, Pfizer Inc., Shanghai, China; Ao Peng – Clinical Pharmacology, Development China, Pfizer Inc., Beijing, China

Objectives: Elranatamab is a T-cell redirecting bispecific antibody targeting both B-cell Maturation Antigen (BCMA) and T-cell co-receptor cluster of differentiation 3 approved for treatment of adult patients with relapsed or refractory multiple myeloma (RRMM). A phase 1b/2 study (C1071008) to evaluate the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of elranatamab in Chinese patients with RRMM had been conducted. This analysis aims to characterize elranatamab PK in Chinese patients and to compare exposures between Chinese and non-Chinese to support the dosing regimen in Chinese patients.

Methods: A previously developed semi-mechanistic 2 compartment target-binding population PK model with first-order absorption [1] was used to fit the PK data from C1071008. NONMEM $PRIOR subroutine was implemented to inform parameter estimation [2]. Different prior weights were considered to minimize the influence of data from non-Chinese subjects while allowing a stable estimation of critical model parameters for Chinese data. Monte Carlo simulation was used to predict exposures in Chinese patients (n=1000) under the approved dosing regimen (12 mg step-up dose 1 on day 1, 32 mg step-up dose 2 on day 4, followed by the first treatment dose of 76 mg on day 8, and 76 mg weekly thereafter through week 24. Responders may switch to biweekly at week 25 onward). Covariates were sampled from a multivariate normal density based on covariance of age and weight observed in C1071008. Exposures were then compared among Chinese, other Asian, and non-Asian patients.

Results: A total of 1555 observations including 412/372 observations for total/free drug and 444/327 observations for total/free soluble BCMA (sBCMA) from 38 Chinese patients were used in the analysis. Informative priors were implemented on parameters of volume of distribution of sBCMA, inter-compartment clearance, and dissociation constant of elranatamab:sBCMA. The estimate for clearance was driven by the data from Chinese patients using noninformative priors. Elranatamab PK in Chinese patients was adequately described by the model. At the approved dosing regimen, exposures associated with cytokine release syndrome (Cmax after step-up dose 1) and objective response rate (average concentration from day 1 to day 28, Cavg_28day) were comparable among Chinese, other Asian, and non-Asian patients. The steady-state Cavg for weekly and biweekly dosing in responders were also comparable.

Conclusions: Simulation results support the approved dosing regimen of elranatamab in the US and EU for Chinese patients with RRMM.

Citations: [1] U.S. FDA. Multi-Discipline Review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2023/761345Orig1s000MultidisciplineR.pdf. Accessed 16 Dec 2024.
[2] Chan Kwong AHP, Calvier EAM, Fabre D, et al. Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine. J Pharmacokinet Pharmacodyn. 2020;47(5):431-446.

Keywords: Elranatamab, Population pharmacokinetic, PRIOR