Elranatamab Fixed Dosing: A Safe, Effective, and Convenient Dosing Approach.

Abstract

Background: Bispecific T-cell engagers (TCEs) are a promising modality for cancer treatment, and evaluation of dosing strategies, including utilization of body weight-based versus fixed dosing, is essential to ensure optimal therapeutic outcomes. Elranatamab is a bispecific TCE that targets B-cell maturation antigen (BCMA) on multiple myeloma cells and CD on T cells. Elranatamab is approved for relapsed or refractory multiple myeloma (RRMM).

Objective: Evaluate the impact of body weight on the pharmacokinetics (PK), safety, and efficacy of elranatamab.

Patients and methods: Data from the phase 2 MagnetisMM-3 trial (NCT04649359) were used to evaluate the impact of body weight on the PK, safety, and efficacy of elranatamab. This trial comprised two cohorts: cohort A included patients who had not previously received BCMA-directed therapy and cohort B included patients who had received prior BCMA-directed therapies. All patients received a 76-mg fixed dose of subcutaneous elranatamab once weekly after a two-step priming dose regimen. Blood samples were collected from MagnetisMM-3 trial patients for PK analysis. This study analyzed the PK, efficacy, and safety of elranatamab across body weight quartiles.

Results: The results demonstrated that when elranatamab was given at a fixed dose, the predose concentrations showed overlapping distributions with comparable medians, especially across the lowest three body weight quartiles, with a lower median for quartile 4, which was not considered clinically relevant. There were no clinically relevant differences in the safety profile between different body weight quartiles. With respect to efficacy, the overall response and complete response rates were comparable across body weight quartiles. A clinically meaningful objective response rate benefit with overlapping confidence intervals was observed across all four quartiles, consistent with the primary efficacy analysis. No trend was identified between body weight and progression-free survival and the duration of response on the basis of the Kaplan-Meier curves.

Conclusions: Concerns with flat dosing include the potential for overdosing those with lower body weights and underdosing individuals with higher body weights. However, this study provides evidence that fixed dosing of elranatamab is effective and demonstrated a consistent and manageable safety profile across a broad range of body weights. There is no significant impact of body weight on the PK, safety, or efficacy of elranatamab. These findings support the approved fixed dosing of elranatamab in patients with RRMM.

Clinicaltrials:

Gov identifier: NCT04649359.