PII-051 - ELRANATAMAB INTEGRATED EXPOSURE-RESPONSE (ER) EFFICACY AND SAFETY ANALYSES IN RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM) USING A CLINICAL UTILITY INDEX (CUI)

I. Abdelgawad¹, H. Lon², P. Soltantabar², J. Hibma², A. Czibere³, D. Wang², M. Elmeliegy²; ¹University of Minnesota, Minneapolis, MN, United States, ²Pfizer, Inc., San Diego, CA, United States, ³Pfizer, Inc., Cambridge, MA, United States.

Background: Elranatamab (ELRA) is a bispecific antibody comprising a B-cell maturation antigen (BCMA)–binding arm and a CD3-binding arm. ELRA was granted approval in the United Stated based on the results of the C1071003 (NCT04649359) study, which indicated deep and durable responses in patients (pts) with RRMM. The recommended dose is 76 mg SC once weekly (QW), following a 2 step-up priming dose regimen, which is reduced to 76 mg SC every 2 weeks (Q2W) after ≥24 weeks for pts who achieved a response. The current analysis was conducted to (a) derive a CUI that integrates ER relationships for efficacy and safety and (b) use the CUI to evaluate the adequacy of the 76-mg QW full treatment dose.

Methods: ER analyses were conducted using data from monotherapy studies: C1071001, C1071002, C1071003, and C1071009. These studies included a dose range of 0.1 μg/kg IV to 1000 μg/kg (ie, 76 mg) QW SC. Separate binomial regression models assessed the relationship between exposure and efficacy endpoint, objective response rate (ORR) as determined by investigator, and safety endpoints of grade ≥3 neutropenia and grade ≥3 infections. Individual exposure metrics (free C_avg,Day28) were obtained using a population PK model.¹ The CUI was derived across the range of free C_avg,Day28. Different weighing scenarios ranged from equal weights for efficacy and safety (ie, 1:1) to higher weight on efficacy vs safety (ie, 4:1).

Results: Free C_avg,Day28 was strongly associated with ORR. Although free C_avg,Day28 was statistically associated with the evaluated safety endpoints, the relationship was relatively flat within the efficacious dose range (215-1000 μg/kg) (Fig. A). Extramedullary disease [EMD] status and number of prior lines of therapy (>5 vs ≤5) were significant covariates for efficacy, and no other covariates were identified for safety. Using different weights changed the magnitude of CUI, without influencing the shape of the CUI (Fig. B). In pts without EMD and with ≤5 prior lines (representing 50% of the pts), 76 mg QW provided ≈90% of maximum CUI, while the next lower dose, 44 mg QW, provided ≈20% of maximum CUI.

Conclusion: The ELRA 76-mg QW regimen provided the highest CUI among all evaluated regimens. The results support the 76-mg QW regimen, which balances maximizing efficacy without increasing the probability of adverse events.