Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study
Safety and efficacy of mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study
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DOI：
10.1016/s1470-2045(22)00335-7
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发表时间：
2022-07-25
期刊：
影响因子：
51.1
通讯作者：
Bartlett, Nancy L.
中科院分区：
文献类型：
--
作者：
Budde, Lihua E.;Sehn, Laurie H.;Bartlett, Nancy L.
莫舒妥珠单抗是一种CD 20 x CD 3 T细胞结合双特异性单克隆抗体，可重定向T细胞以消除恶性B细胞。在一项1期研究中，mosunetuzumab在复发性或难治性B细胞淋巴瘤患者中耐受性良好且具有活性。因此，我们的目的是评估固定持续时间mosunetuzumab在接受过两种或更多种既往治疗的复发性或难治性滤泡性淋巴瘤患者中的安全性和抗肿瘤活性。方法：我们在7个国家（澳大利亚、加拿大、德国、韩国、西班牙、英国和美国）的49个中心进行了一项单臂、多中心、2期研究。所有患者均为18岁或以上，经组织学证实为滤泡性淋巴瘤（1-3a级），东部肿瘤协作组体能状态评分为0-1。患者患有复发性疾病或对两种或更多种既往治疗线（包括抗CD 20治疗和烷化剂）难治性疾病。静脉注射莫舒妥珠单抗以21天为一个周期，周期1递增给药：周期1第1天1 mg，周期1第8天2 mg，周期1第15天和周期2第1天60 mg，周期3第1天及以后30 mg。研究者使用人用药品注册技术要求国际协调项目标准评估为完全缓解的患者在第8周期后完成治疗，而部分缓解或疾病稳定的患者继续治疗长达17个周期。主要终点是所有入组患者中独立审查委员会评估的完全缓解率（作为最佳缓解）;主要疗效分析比较了在接受泛I类PI 3 K抑制剂copanlisib的相似患者人群中观察到的IRC评估的完全缓解率与14%的历史对照完全缓解率。在所有入组患者中评估安全性。本研究在ClinicalTrials.gov注册，编号NCT 02500407，目前正在进行中。在2019年5月2日至2020年9月25日期间，我们招募了90名患者。截至数据截止日期（2021年8月27日），中位随访时间为18.3个月（IQR 13.8-23.3）。根据独立审查委员会的评估，54例患者（60. 0%[95% CI 49. 1 - 70. 2]）记录了完全缓解。观察到的完全缓解率显著高于copanlisib的历史对照完全缓解率14%（p
Background Mosunetuzumab is a CD20 x CD3 T-cell-engaging bispecific monoclonal antibody that redirects T cells to eliminate malignant B cells. In a phase 1 study, mosunetuzumab was well tolerated and active in patients with relapsed or refractory B-cell lymphoma. We, therefore, aimed to evaluate the safety and anti-tumour activity of fixed -duration mosunetuzumab in patients with relapsed or refractory follicular lymphoma who had received two or more previous therapies. Methods We conducted a single-arm, multicentre, phase 2 study at 49 centres in seven countries (Australia, Canada, Germany, South Korea, Spain, UK, and USA). All patients were aged 18 years or older with histologically confirmed follicular lymphoma (grade 1-3a) and an Eastern Cooperative Oncology Group performance status of 0-1. Patients had disease that was relapsed or refractory to two or more previous lines of treatment, including an anti-CD20 therapy and an alkylating agent. Intravenous mosunetuzumab was administered in 21-day cycles with cycle 1 step-up dosing: 1 mg on cycle 1 day 1, 2 mg on cycle 1 day 8, 60 mg on cycle 1 day 15 and cycle 2 day 1, and 30 mg on day 1 of cycle 3 and onwards. Patients with a complete response by investigator assessment using the International Harmonisation Project criteria completed treatment after cycle 8, whereas patients with a partial response or stable disease continued treatment for up to 17 cycles. The primary endpoint was independent review committee-assessed complete response rate (as best response) in all enrolled patients; the primary efficacy analysis compared the observed IRC-assessed complete response rate with a 14% historical control complete response rate in a similar patient population receiving the pan class I PI3K inhibitor copanlisib. Safety was assessed in all enrolled patients. This study is registered with ClinicalTrials.gov, number NCT02500407, and is ongoing. Findings Between May 2, 2019, and Sept 25, 2020, we enrolled 90 patients. As of the data cutoff date (Aug 27, 2021), the median follow-up was 18.3 months (IQR 13.8-23.3). According to independent review committee assessment, a complete response was recorded in 54 patients (60.0% [95% CI 49.1-70.2]). The observed complete response rate was significantly higher than the historical control complete response rate with copanlisib of 14% (p