Elranatamab is a heterodimeric humanized full-length bispecific antibody composed of one B-cell maturation antigen (BCMA) binding arm and one cluster of differentiation 3 (CD3) binding arm. Results from the MagnetisMM-3 study indicated deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM). The current analysis was conducted to characterize the relationship between free (i.e., unbound) elranatamab exposure and objective response rate (ORR), complete response rate (CRR), progression-free survival (PFS), and duration of response (DOR), and the impact of potential covariates on these exposure-response (E-R) relationships. Data from four clinical studies and a wide dosing range were used for the E-R analysis. The E-R analyses of ORR and CRR were conducted by binomial logistic regression method, whereas Kaplan-Meier (KM) curves and Cox proportional hazards (PH) model were used for PFS and DOR. The analysis included data from 312 response-evaluable patients. The results suggested that higher elranatamab exposure and lower soluble BCMA (sBCMA) were associated with higher probability of achieving objective response (OR) and complete response (CR). For PFS, higher exposure was associated with longer PFS, which is driven by rapid responses or progression events within the initial treatment cycles. At later time points, a flat relationship between exposure and PFS was observed. No E-R relationship was identified for DOR. The current analyses support the approved initial dosing regimen of elranatamab and the dosing switch to less frequent dosing in responding patients during later treatment cycles. NCT03269136, NCT04798586, NCT04649359, and NCT05014412.
Lon et al. (Mon,) studied this question.