Department of Hematology, National Cancer Center Hospital, Tokyo, Japan.
Department of Hematology Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
Jpn J Clin Oncol. 2023 Oct 4;53(10):912-921. doi: 10.1093/jjco/hyad082.
This dose-escalation part of an ongoing Phase I study assessed the tolerability, safety and pharmacokinetics of mosunetuzumab in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL).
Mosunetuzumab was administered intravenously, with step-up dosing in a 3 + 3 design, on Days 1, 8 and 15 of Cycle 1, and Day 1 of each subsequent 21-day cycle for up to 17 cycles to patients across five cohorts with different target doses (2.8, 6.0, 13.5, 27.0 or 60.0 mg).
As of 5 July 2022, 23 patients had received mosunetuzumab. The median patient age was 63.0 years, 56.5% of patients were male, and 69.6% of patients had diffuse large B-cell lymphoma, 17.4% had transformed follicular lymphoma (FL) and 13.0% had FL. The median number of prior lines of therapy was 4. Mosunetuzumab was well tolerated and there were no deaths. The most common adverse events (any grade) were neutropenia/neutrophil count decreased (47.8%) and cytokine release syndrome (34.8%). Most cytokine release syndrome events were Grade 1/2 (one Grade 3), and most occurred within 24 hours of the first dose of mosunetuzumab. The apparent half-life of mosunetuzumab was 4.1-5.0 days. Two patients achieved a complete response, and 11 patients achieved a partial response.
This study demonstrated that mosunetuzumab has an acceptable safety profile and antitumor activity in Japanese patients with relapsed/refractory B-cell NHL. The recommended Phase II dose of 1.0/2.0/60.0/60.0/30.0 mg was tolerable and there were no new or different safety signals compared with the global Phase I study.
本研究为正在进行的 I 期研究的剂量递增部分，旨在评估 mosunetuzumab 在日本复发/难治性 B 细胞非霍奇金淋巴瘤（NHL）患者中的耐受性、安全性和药代动力学。
在这项 5 个队列的研究中，mosunetuzumab 采用 3+3 设计，静脉输注，在第 1 周期第 1、8 和 15 天，以及随后每个 21 天周期的第 1 天给药，最多给药 17 个周期，目标剂量分别为 2.8、6.0、13.5、27.0 和 60.0mg。
截至 2022 年 7 月 5 日，23 例患者接受了 mosunetuzumab 治疗。患者中位年龄为 63.0 岁，56.5%为男性，69.6%为弥漫性大 B 细胞淋巴瘤，17.4%为转化滤泡淋巴瘤（FL），13.0%为 FL。中位治疗线数为 4 线。mosunetuzumab 耐受性良好，无死亡病例。最常见的任何等级的不良事件为中性粒细胞减少症/中性粒细胞计数减少（47.8%）和细胞因子释放综合征（34.8%）。大多数细胞因子释放综合征事件为 1/2 级（1 例为 3 级），且大多数发生在 mosunetuzumab 首次给药后 24 小时内。mosunetuzumab 的表观半衰期为 4.1-5.0 天。2 例患者达到完全缓解，11 例患者达到部分缓解。
本研究表明，mosunetuzumab 在日本复发/难治性 B 细胞 NHL 患者中具有可接受的安全性和抗肿瘤活性。与全球 I 期研究相比，推荐的 1.0/2.0/60.0/60.0/30.0mg 剂量是可耐受的，且没有新的或不同的安全性信号。
