Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR™ therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients.
Phase 1b study of otlertuzumab (TRU-016), an anti-CD37 monospecific ADAPTIR™ therapeutic protein, in combination with rituximab and bendamustine in relapsed indolent lymphoma patients.
复制标题
DOI：
10.1007/s10637-014-0125-2
复制
发表时间：
2014-12
影响因子：
3.4
通讯作者：
Goy, Andre
中科院分区：
文献类型：
--
作者：
Gopal, Ajay K.;Tarantolo, Stefano R.;Bellam, Naresh;Green, Damian J.;Griffin, Melissa;Feldman, Tatyana;Mato, Anthony R.;Eisenfeld, Amy J.;Stromatt, Scott C.;Goy, Andre
CD 37是存在于正常和恶性B细胞上的细胞表面四跨膜蛋白。Otlertuzumab（TRU-016）是一种新型人源化抗CD 37蛋白治疗剂，其触发恶性B细胞的直接半胱天冬酶非依赖性凋亡并诱导抗体依赖性细胞介导的细胞毒性。本研究评价了Otlertuzumab联合利妥昔单抗和苯达莫司汀治疗复发性惰性B细胞非霍奇金淋巴瘤（NHL）患者的安全性、药代动力学和疗效。复发性或难治性NHL患者在第1天和第15天静脉内（IV）接受奥勒妥珠单抗（10或20 mg/kg），在第1天和第2天接受苯达莫司汀（90 mg/m2），并且在第1天接受利妥昔单抗（375 mg/m2），持续长达6个28天周期。使用标准标准确定响应。12例患者接受治疗，每个剂量水平6例患者;中位年龄为57岁（范围：51-79），既往治疗方案的中位数量为3（范围：1-4）。所有患者均在既往利妥昔单抗治疗后复发，包括7例最近一次治疗难治性患者。在10和20 mg/kg剂量队列中，首次给药后的平均半衰期分别为8和10天，12次给药后的平均半衰期分别为12或14天。总有效率为83%（10/12），4例CR（32%）。最常见的不良事件是中性粒细胞减少症、恶心、疲乏、白细胞减少症和失眠;大多数为1级或2级。Otlertuzumab联合利妥昔单抗和苯达莫司汀耐受性良好，并在大多数复发性惰性B-NHL患者中诱导应答。
CD37 is cell surface tetraspanin present on normal and malignant B cells. Otlertuzumab (TRU-016) is a novel humanized anti-CD37 protein therapeutic that triggers direct caspase independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. This study evaluated the safety, pharmacokinetics, and efficacy of otlertuzumab administered in combination with rituximab and bendamustine to patients with relapsed, indolent B-cell non-Hodgkin Lymphoma (NHL). Patients with relapsed or refractory NHL received otlertuzumab (10 or 20 mg/kg) intravenously (IV) on days 1 and 15, bendamustine (90 mg/m2) on days 1 and 2, and rituximab (375 mg/m2) on day 1 for up to six 28 day cycles. Responses were determined using standard criteria. Twelve patients were treated with 6 patients at each dose level; median age was 57 years (range, 51–79), and median number of prior regimens was 3 (range, 1–4). All patients had relapsed after prior rituximab including 7 refractory to their most recent previous treatment. In the 10 and 20 mg/kg dose cohorts, the mean half-life was 8 and 10 days following the first dose, and 12 or 14 days following 12 doses of otlertuzumab, respectively. Overall response rate was 83 % (10/12) with 4 CRs (32 %). The most frequent adverse events were neutropenia, nausea, fatigue, leukopenia, and insomnia; most were grade 1 or 2. Otlertuzumab in combination with rituximab and bendamustine was well tolerated and induced responses in the majority of patients with relapsed indolent B-NHL.
登录
查看更多内容
影响因子：
3.6
作者：
Leoni, Lorenzo M.;Hartley, John A.
通讯作者：
Hartley, John A.
影响因子：
20.3
作者：
Caruso, Vanesa;Di Castelnuovo, Augusto;Donati, Maria Benedetta
通讯作者：
Donati, Maria Benedetta
影响因子：
20.3
作者：
Byrd, John C.;Pagel, John M.;Furman, Richard R.
通讯作者：
Furman, Richard R.
影响因子：
20.3
作者：
Kennedy, AD;Solga, MD;Taylor, RP
通讯作者：
Taylor, RP
影响因子：
7.3
作者：
MOORE, K;COOPER, SA;JONES, DB
通讯作者：
JONES, DB