Mosunetuzumab
(Synonyms: BTCT-4465A) 目录号 : GC66351
Mosunetuzumab (BTCT-4465A) 是一种人源化、基于免疫球蛋白 G1 的双特异性抗体，靶向 CD20 (B 细胞) 和 CD3 (T 细胞)。Mosunetuzumab 重定向 T 细胞以接合和消除恶性 B 细胞，可用于研究复发或难治性 (R/R) B 细胞非霍奇金淋巴瘤 (B-NHL)。
Cas No.:1905409-39-3
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Mosunetuzumab (BTCT-4465A) is a humanized, immunoglobulin G1-based bispecific antibody targeting CD20 (B cells) and CD3 (T cells). Mosunetuzumab redirects T cells to engage and eliminate malignant B cells and can be used for the research of relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs)[1].
| Cas No. | 1905409-39-3 | SDF | Download SDF |
| 别名 | BTCT-4465A | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at -20°C | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Safety and efficacy of Mosunetuzumab, a bispecific antibody, in patients with relapsed or refractory follicular lymphoma: a single-arm, multicentre, phase 2 study
Lancet Oncol 2022 Aug;23(8):1055-1065.PMID:35803286DOI:10.1016/S1470-2045(22)00335-7.
Background: Mosunetuzumab is a CD20 × 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<0·0001), thereby meeting the primary study endpoint. Cytokine release syndrome was the most common adverse event (40 [44%] of 90 patients) and was predominantly grade 1 (23 [26%] of 90) and grade 2 (15 [17%]), and primarily confined to cycle 1. The most common grade 3-4 adverse events were neutropenia or neutrophil count decreased (24 [27%] of 90 patients), hypophosphataemia (15 [17%]), hyperglycaemia (seven [8%]), and anaemia (seven [8%]). Serious adverse events occurred in 42 (47%) of 90 patients. No treatment-related grade 5 (ie, fatal) adverse event occurred. Interpretation: Fixed-duration Mosunetuzumab has a favourable safety profile and induces high rates of complete remissions, allowing potential administration as an outpatient regimen, in patients with relapsed or refractory follicular lymphoma and two or more previous therapies. Funding: F Hoffmann-La Roche and Genentech.
Single-Agent Mosunetuzumab Shows Durable Complete Responses in Patients With Relapsed or Refractory B-Cell Lymphomas: Phase I Dose-Escalation Study
J Clin Oncol 2022 Feb 10;40(5):481-491.PMID:34914545DOI:10.1200/JCO.21.00931.
Purpose: Mosunetuzumab is a bispecific antibody targeting CD20 and CD3 that redirects T cells to engage and eliminate malignant B cells and is being developed for relapsed or refractory (R/R) B-cell non-Hodgkin lymphomas (B-NHLs). Methods: This first-in-human trial (ClinicalTrials.gov identifier: NCT02500407) evaluated the safety and tolerability and efficacy of Mosunetuzumab in patients with R/R B-NHL and established the recommended phase II dose. Data from dose escalation are presented. Single-agent Mosunetuzumab was administered intravenously in 3-week cycles, at full dose in cycle 1 day 1 (group A) or with ascending (step-up) doses during cycle 1 on days 1, 8, and 15 (group B), for eight or 17 cycles on the basis of tumor response. Results: Two hundred thirty patients were enrolled. Doses up to 2.8 mg and 60 mg were assessed in groups A and B, respectively; maximum tolerated dose was not exceeded. In group B (n = 197), common adverse events (≥ 20% of patients) were neutropenia (28.4%), cytokine release syndrome (27.4%), hypophosphatemia (23.4%), fatigue (22.8%), and diarrhea (21.8%). Cytokine release syndrome was mostly low-grade (grade ≥ 3: 1.0%) and mainly confined to cycle 1. Across the doses investigated (group B), best overall response rates were 34.9% and 66.2% in patients with aggressive and indolent B-NHL, respectively, and complete response rates were 19.4% and 48.5%. Among patients with a complete response, the median duration of response was 22.8 months (95% CI, 7.6 to not estimable) and 20.4 (95% CI, 16 to not estimable) in patients with aggressive and indolent B-NHL, respectively. Conclusion: Mosunetuzumab, administered with step-up dosing, has a manageable safety profile and induces durable complete responses in R/R B-NHL. The expansion stage of the study is ongoing at the dose level of 1/2/60/60/30 mg selected for further study.
Mosunetuzumab: First Approval
Drugs 2022 Jul;82(11):1229-1234.PMID:35947358DOI:10.1007/s40265-022-01749-5.
Mosunetuzumab (Lunsumio®), an anti-CD20/CD3 T-cell engaging bispecific antibody, is being developed by Roche for the treatment of relapsed or refractory follicular lymphoma. Mosunetuzumab was recently conditionally approved in the EU for the treatment of relapsed or refractory follicular lymphoma in adults who have received at least two prior systemic therapies. This article summarizes the milestones in the development of Mosunetuzumab leading to this first approval for relapsed or refractory follicular lymphoma.
Mitigating the risk of cytokine release syndrome in a Phase I trial of CD20/CD3 bispecific antibody Mosunetuzumab in NHL: impact of translational system modeling
NPJ Syst Biol Appl 2020 Aug 28;6(1):28.PMID:32859946DOI:10.1038/s41540-020-00145-7.
Mosunetuzumab, a T-cell dependent bispecific antibody that binds CD3 and CD20 to drive T-cell mediated B-cell killing, is currently being tested in non-Hodgkin lymphoma. However, potent immune stimulation with T-cell directed therapies poses the risk of cytokine release syndrome, potentially limiting dose and utility. To understand mechanisms behind safety and efficacy and explore safety mitigation strategies, we developed a novel mechanistic model of immune and antitumor responses to the T-cell bispecifics (Mosunetuzumab and blinatumomab), including the dynamics of B- and T-lymphocytes in circulation, lymphoid tissues, and tumor. The model was developed and validated using Mosunetuzumab nonclinical and blinatumomab clinical data. Simulations delineated mechanisms contributing to observed cell and cytokine (IL6) dynamics and predicted that initial step-fractionated dosing limits systemic T-cell activation and cytokine release without compromising tumor response. These results supported a change to a step-fractionated treatment schedule of Mosunetuzumab in the ongoing Phase I clinical trial, enabling safer administration of higher doses.
Bispecific Antibodies for Non-Hodgkin Lymphoma Treatment
Curr Treat Options Oncol 2022 Feb;23(2):155-170.PMID:35182296DOI:10.1007/s11864-021-00925-1.
While there have been numerous advances in the field of non-Hodgkin lymphoma (NHL) over the last decade, relapsed and/or refractory (R/R) NHL remains a challenge and an area with unmet needs. T-cell redirecting immunotherapeutic approaches including chimeric antigen receptor (CAR) T-cells and bispecific antibodies (BsAbs) have the potential to revolutionize NHL therapy. BsAbs target CD3 on T-cells and CD19 or CD20 on malignant B-cells and have shown promises as a novel immunotherapy for NHL. The development of CD19 × CD3 BsAbs such as blinatumomab was met with significant challenges due to dose-limiting neurologic side effects. However, several CD20 × CD3 BsAbs including odronextamab, Mosunetuzumab, glofitamab, and epcoritamab emerged recently. They have favorable toxicity profiles, with reduced cytokine release syndrome and neurotoxicity. In addition, all these BsAbs have demonstrated very promising efficacy in R/R NHL. With expansion and registrational studies actively ongoing, approvals of these agents for R/R NHL are anticipated in the near future. Some important questions pertinent to future clinical development of BsAbs include when and how to best utilize BsAbs in the management of R/R NHL, whether there is a role of BsAbs in treatment-naïve NHL, and how to combine BsAbs with other therapies. For example, whether BsAbs can be combined with cytotoxic chemotherapy effectively remains to be seen. A plethora of clinical studies will be needed to help address these questions, some of which are already ongoing. In addition, how do BsAbs compare to CAR T-cell therapy and how to choose and sequence between BsAbs and CAR T-cell therapy need to be addressed. While many of these critical questions remain to be answered in clinical studies, we believe the future of BsAbs in the NHL is very bright.