Elmeliegy Mohamed, Soltantabar Pooneh, Hibma Jennifer, Ashman Olivia, Wang Diane, Lon Hoi-Kei
Oncology Research and Development, Pfizer, Inc., San Diego, CA, USA.
Pfizer Research and Development, Pfizer, Inc., San Diego, CA, USA.
Target Oncol. 2025 Aug 19. doi: 10.1007/s11523-025-01170-4.
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).
Evaluate the impact of body weight on the pharmacokinetics (PK), safety, and efficacy of elranatamab.
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.
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.
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.
NCT04649359.
双特异性T细胞衔接器（TCE）是一种很有前景的癌症治疗方式，评估给药策略，包括基于体重给药与固定剂量给药的应用，对于确保最佳治疗效果至关重要。埃拉纳单抗是一种双特异性TCE，可靶向多发性骨髓瘤细胞上的B细胞成熟抗原（BCMA）和T细胞上的CD。埃拉纳单抗已被批准用于复发或难治性多发性骨髓瘤（RRMM）。
评估体重对埃拉纳单抗的药代动力学（PK）、安全性和疗效的影响。
来自2期MagnetisMM-3试验（NCT04649359）的数据用于评估体重对埃拉纳单抗的PK、安全性和疗效的影响。该试验包括两个队列：队列A包括之前未接受过BCMA导向治疗的患者，队列B包括之前接受过BCMA导向治疗的患者。所有患者在经过两步诱导剂量方案后，每周皮下注射一次76mg固定剂量的埃拉纳单抗。从MagnetisMM-3试验患者中采集血样进行PK分析。本研究分析了埃拉纳单抗在不同体重四分位数中的PK、疗效和安全性。
结果表明，当以固定剂量给予埃拉纳单抗时，给药前浓度显示出重叠分布，中位数相当，尤其是在最低的三个体重四分位数中，四分位数4的中位数较低，但这在临床上不被认为具有相关性。不同体重四分位数之间的安全性概况没有临床相关差异。在疗效方面，不同体重四分位数的总体缓解率和完全缓解率相当。在所有四个四分位数中均观察到具有重叠置信区间的具有临床意义的客观缓解率益处，这与主要疗效分析一致。根据Kaplan-Meier曲线，未发现体重与无进展生存期和缓解持续时间之间存在趋势。
固定剂量给药的问题包括体重较低者可能用药过量，体重较高者可能用药不足。然而，本研究提供的证据表明，埃拉纳单抗固定剂量给药是有效的，并且在广泛的体重范围内显示出一致且可控的安全性概况。体重对埃拉纳单抗的PK、安全性或疗效没有显著影响。这些发现支持在RRMM患者中批准的埃拉纳单抗固定剂量给药。
NCT04649359。
