Isatuximab
(Synonyms: 艾萨妥昔单抗) 目录号 : GC63386
Isatuximab (anti-CD38) (SAR650984, hu38SB19) is an IgG1-derived monoclonal antibody that binds to a specific extracellular epitope of CD38 receptor with a kd of 0.12 nM.
Cas No.:1461640-62-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Isatuximab (anti-CD38) (SAR650984, hu38SB19) is an IgG1-derived monoclonal antibody that binds to a specific extracellular epitope of CD38 receptor with a kd of 0.12 nM.
[1] Meletios Dimopoulos, et al. Blood . 2021 Mar 4;137(9):1154-1165. [2] Swiss Public Assessment Report. Date: 7 May 2020.
| Cas No. | 1461640-62-9 | SDF | |
| 别名 | 艾萨妥昔单抗 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at 4°C, do not freeze | |
| 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。
Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial
Lancet 2021 Jun 19;397(10292):2361-2371.PMID:34097854DOI:10.1016/S0140-6736(21)00592-4.
Background: Isatuximab is an anti-CD38 monoclonal antibody approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone for relapsed or refractory multiple myeloma. This phase 3, open-label study compared the efficacy of Isatuximab plus carfilzomib-dexamethasone versus carfilzomib-dexamethasone in patients with relapsed multiple myeloma. Methods: This was a prospective, randomised, open-label, parallel-group, phase 3 study done at 69 study centres in 16 countries across North America, South America, Europe, and the Asia-Pacific region. Patients with relapsed or refractory multiple myeloma aged at least 18 years who had received one to three previous lines of therapy and had measurable serum or urine M-protein were eligible. Patients were randomly assigned (3:2) to Isatuximab plus carfilzomib-dexamethasone (Isatuximab group) or carfilzomib-dexamethasone (control group). Patients in the Isatuximab group received Isatuximab 10 mg/kg intravenously weekly for the first 4 weeks, then every 2 weeks. Both groups received the approved schedule of intravenous carfilzomib and oral or intravenous dexamethasone. Treatment continued until progression or unacceptable toxicity. The primary endpoint was progression-free survival and was assessed in the intention-to-treat population according to assigned treatment. Safety was assessed in all patients who received at least one dose according to treatment received. The study is registered at ClinicalTrials.gov, NCT03275285. Findings: Between Nov 15, 2017, and March 21, 2019, 302 patients with a median of two previous lines of therapy were enrolled. 179 were randomly assigned to the Isatuximab group and 123 to the control group. Median progression-free survival was not reached in the Isatuximab group compared with 19·15 months (95% CI 15·77-not reached) in the control group, with a hazard ratio of 0·53 (99% CI 0·32-0·89; one-sided p=0·0007). Treatment-emergent adverse events (TEAEs) of grade 3 or worse occurred in 136 (77%) of 177 patients in the Isatuximab group versus 82 (67%) of 122 in the control group, serious TEAEs occurred in 105 (59%) versus 70 (57%) patients, and TEAEs led to discontinuation in 15 (8%) versus 17 (14%) patients. Fatal TEAEs during study treatment occurred in six (3%) versus four (3%) patients. Interpretation: The addition of Isatuximab to carfilzomib-dexamethasone significantly improves progression-free survival and depth of response in patients with relapsed multiple myeloma, representing a new standard of care for this patient population. Funding: Sanofi. VIDEO ABSTRACT.
Isatuximab: A Review of Its Use in Multiple Myeloma
Target Oncol 2021 Sep;16(5):675-686.PMID:34351561DOI:10.1007/s11523-021-00827-0.
Isatuximab (Sarclisa®; isatuximab-irfc in the USA) is an anti-CD38 monoclonal antibody (mAb) approved for use in the treatment of adults with multiple myeloma (MM): in combination with pomalidomide and dexamethasone for those with relapsed and refractory MM (RRMM) who have received ≥ 2 prior therapies, including lenalidomide and a proteasome inhibitor; and in combination with carfilzomib and dexamethasone for those with relapsed MM who have received ≥ 1 prior therapy. In phase III studies, the addition of Isatuximab to pomalidomide and dexamethasone significantly prolonged progression-free survival (PFS) and improved the depth of tumour response in patients with RRMM, as did the addition of Isatuximab to carfilzomib and dexamethasone in patients with relapsed or refractory MM. Health-related quality of life was maintained when Isatuximab was combined with these other therapies. Isatuximab-based combination therapies were generally well tolerated and demonstrated a manageable safety profile with no new safety signals. Although mature overall survival data are awaited, available evidence indicates that the combinations of Isatuximab with pomalidomide and dexamethasone and Isatuximab with carfilzomib and dexamethasone are important additional treatment options for RRMM and relapsed MM, respectively.
Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study
Lancet 2019 Dec 7;394(10214):2096-2107.PMID:31735560DOI:10.1016/S0140-6736(19)32556-5.
Background: Isatuximab is a monoclonal antibody that binds a specific epitope on the human CD38 receptor and has antitumour activity via multiple mechanisms of action. In a previous phase 1b study, around 65% of patients with relapsed and refractory multiple myeloma achieved an overall response with a combination of Isatuximab with pomalidomide and low-dose dexamethasone. The aim of this study was to determine the progression-free survival benefit of Isatuximab plus pomalidomide and dexamethasone compared with pomalidomide and dexamethasone in patients with relapsed and refractory multiple myeloma. Methods: We did a randomised, multicentre, open-label, phase 3 study at 102 hospitals in 24 countries in Europe, North America, and the Asia-Pacific regions. Eligible participants were adult patients with relapsed and refractory multiple myeloma who had received at least two previous lines of treatment, including lenalidomide and a proteasome inhibitor. Patients were excluded if they were refractory to previous treatment with an anti-CD38 monoclonal antibody. We randomly assigned patients (1:1) to either Isatuximab 10 mg/kg plus pomalidomide 4 mg plus dexamethasone 40 mg (20 mg for patients aged ≥75 years), or pomalidomide 4 mg plus dexamethasone 40 mg. Randomisation was done using interactive response technology and stratified according to the number of previous lines of treatment (2-3 vs >3) and age (<75 years vs ≥75 years). Treatments were assigned based on a permuted blocked randomisation scheme with a block size of four. The isatuximab-pomalidomide-dexamethasone group received Isatuximab intravenously on days 1, 8, 15, and 22 in the first 28-day cycle, then on days 1 and 15 in subsequent cycles. Both groups received oral pomalidomide on days 1 to 21 in each cycle, and oral or intravenous dexamethasone on days 1, 8, 15, and 22 of each cycle. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal. Dose reductions for adverse reactions were permitted for pomalidomide and dexamethasone, but not for Isatuximab. The primary endpoint was progression-free survival, determined by an independent response committee and assessed in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, number NCT02990338. Findings: Between Jan 10, 2017, and Feb 2, 2018, we randomly assigned 307 patients to treatment: 154 to isatuximab-pomalidomide-dexamethasone, and 153 to pomalidomide-dexamethasone. At a median follow-up of 11·6 months (IQR 10·1-13·9), median progression-free survival was 11·5 months (95% CI 8·9-13·9) in the isatuximab-pomalidomide-dexamethasone group versus 6·5 months (4·5-8·3) in the pomalidomide-dexamethasone group; hazard ratio 0·596, 95% CI 0·44-0·81; p=0·001 by stratified log-rank test. The most frequent treatment-emergent adverse events (any grade; isatuximab-pomalidomide-dexamethasone vs pomalidomide-dexamethasone) were infusion reactions (56 [38%] vs 0), upper respiratory tract infections (43 [28%] vs 26 [17%]), and diarrhoea (39 [26%] vs 29 [20%]). Adverse events with a fatal outcome were reported in 12 patients (8%) in the isatuximab-pomalidomide-dexamethasone group and 14 (9%) in the pomalidomide-dexamethasone group. Deaths due to treatment-related adverse events were reported for one patient (<1%) in the isatuximab-pomalidomide-dexamethasone group (sepsis) and two (1%) in the pomalidomide-dexamethasone group (pneumonia and urinary tract infection). Interpretation: The addition of Isatuximab to pomalidomide-dexamethasone significantly improves progression-free survival in patients with relapsed and refractory multiple myeloma. Isatuximab is an important new treatment option for the management of relapsed and refractory myeloma, particularly for patients who become refractory to lenalidomide and a proteasome inhibitor. Funding: Sanofi. VIDEO ABSTRACT.
Isatuximab in the Treatment of Multiple Myeloma: A Review and Comparison With Daratumumab
Technol Cancer Res Treat 2022 Jan-Dec;21:15330338221106563.PMID:35903924DOI:10.1177/15330338221106563.
Multiple myeloma (MM) is a hematologic malignancy characterized by the proliferation of clonal plasma cells. Although advances in treatment have markedly improved survival outcomes for patients with MM, this disease is still considered incurable owing to its high incidence of relapse and refractoriness. Isatuximab is an anti-CD38 monoclonal antibody that can induce apoptosis in myeloma cells through a variety of mechanisms. Many clinical studies have demonstrated the efficacy and efficiency of Isatuximab in both relapsed/refractory multiple myeloma (RRMM) and newly diagnosed multiple myeloma, leading to its approval for the treatment of adults with RRMM in combination therapies. In this review, the structure, mechanisms of action, pharmacokinetics, pharmacogenetics, and safety profile of Isatuximab in MM are summarized. Additionally, Isatuximab is compared with daratumumab in terms of mechanism and efficacy.
Isatuximab: First Approval
Drugs 2020 Jun;80(9):905-912.PMID:32347476DOI:10.1007/s40265-020-01311-1.
Isatuximab (isatuximab-irfc; Sarclisa®) is an IgG1 monoclonal antibody that binds to the glycoprotein CD38 expressed on the surface of haematopoietic and tumour cells. It is being developed by Sanofi, under a license from Immunogen, for the treatment of haematological malignancies. In March 2020, intravenous Isatuximab (in combination with pomalidomide and dexamethasone) was approved in the USA for the treatment of adult patients with multiple myeloma who have received ≥ 2 prior therapies, including lenalidomide and a proteasome inhibitor. Isatuximab has also received a positive opinion in the EU for the treatment of relapsed and refractory multiple myeloma. This article summarizes the milestones in the development of Isatuximab leading to the first approval in the USA.