(PA-045) Elranatamab Fixed Dosing: The Optimal Dosing Strategy for Safety, Efficacy, and Convenience Across Body Weights

Introduction: Bispecific T-cell engagers (TCEs) are a promising modality for cancer treatment, and evaluation of dosing strategies including utilization of body weight (BW)–based versus fixed dosing is essential to ensure optimal therapeutic outcomes. Elranatamab is a bispecific TCE that targets B-cell maturation antigen (BCMA) on myeloma cells and CD3 on T cells. Elranatamab is approved for the treatment of adult patients (pts) with relapsed/refractory multiple myeloma (RRMM). Here, we provide data evaluating the impact of BW on the pharmacokinetics (PK), safety, and efficacy of elranatamab, supporting the approved fixed dosing strategy.

Methods: Data from the phase 2 MagnetisMM-3 trial (NCT04649359) were used to evaluate the impact of BW on the PK, safety, and efficacy of elranatamab. This trial comprised 2 cohorts: Cohort A included pts who had not previously received BCMA-directed therapy and Cohort B included pts who had received prior BCMA-directed therapies. All pts received a 76-mg fixed dose of subcutaneous elranatamab after a 2-step priming dose regimen (12mg on day 1; 32mg on day 4). Blood samples were collected from MagnetisMM-3 trial pts for PK analysis. The PK, safety, and efficacy were assessed using the 20th percentile of BW as a cutoff (ie “low BW” is ≤20th percentile and “high BW” is >20th percentile of BW).

Results: A total of 187 pts (both cohorts) were enrolled in MagnetisMM-3. The median (range) baseline BW was 71.8 kg (36.5-159.6 kg). The 20th percentile of BW was 60.3 kg. In the pts receiving both step-up doses (n=183), median (range) BW in the low (n=37) and high (n=146) BW groups was 54.9 kg (36.5-60.3 kg) and 76.4 kg (61-159.6 kg), respectively. Baseline characteristics were balanced between groups. Elranatamab pre-dose concentrations were similar between the low and high BW groups. There were no clinically relevant differences in the safety profiles between the low and high BW groups (n=183). The overall incidence of adverse events (AEs, both 100%), Grade 3/4 AEs (62.2% vs 71.2%), serious AEs (70.3% vs 76.7%), and discontinuations due to AEs (24.3% vs 28.1%) were similar between the low and high BW groups. The overall response rate (50% vs 64%) and complete response rate (34.6% vs 38.2%) were comparable between low and high BW groups. The Kaplan-Meier (KM) curves for progression-free survival overlapped between groups (P=0.65). The median duration of response was not reached in either group with overlapping KM curves (P=0.74).

Conclusions: Concerns with flat dosing include the potential for overdosing pts with lower BW and underdosing individuals with higher BW. 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 BWs. There is no significant impact of BW on the PK, safety, or efficacy of elranatamab. These findings support the approved fixed dosing of elranatamab in pts with RRMM.