Brentuximab vedotin
(Synonyms: 维布妥昔单抗；本妥昔单抗) 目录号 : GC68296Brentuximab vedotin (cAC10-vcMMAE) 是一种抗体-药物偶联物 (ADC)，由抗 CD30 抗体和 Monomethyl auristatin E (MMAE) 组成。Brentuximab vedotin 抑制 CD30 阳性细胞，其 IC50 值为 2.5 ng/mL。Brentuximab vedotin 可用于复发难治性霍奇金淋巴瘤的研究。
Cas No.:914088-09-8
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
IC50: 2.5 ng/mL (CD30)[2]
Brentuximab vedotin (cAC10-vcMMAE) is an antibody-drug conjugate (ADC) comprising an anti-CD30 antibody and the cytotoxic agent Monomethyl auristatin E (MMAE). Brentuximab vedotin inhibits CD30-positive cells with an IC50 of 2.5 ng/mL. Brentuximab vedotin can be used for the research of relapsed and refractory Hodgkin lymphoma[1][2].
Brentuximab vedotin (cAC10-vcMMAE) (1 μg/mL; 96 h) shows cytotoxicity to CD30+ in Karpas 299 cells[2].
Brentuximab vedotin (CAC10-VCMMAE) (1 μg/mL; 12, 24 and 48 h) selectively induces growth arrest in G2/M phase then lead to apoptotic cell death[2].
Cell Cytotoxicity Assay[2]
| Cell Line: | Karpas 299 cells |
| Concentration: | 1 μg/mL |
| Incubation Time: | 96 h |
| Result: | Showed cytotoxicity to CD30+ Karpas 299 cells with an IC50 value of 2.5 ng/mL. |
Cell Cycle Analysis[2]
| Cell Line: | L540 cells |
| Concentration: | 1 μg/mL |
| Incubation Time: | 12, 24, and 48 h |
| Result: | Selectively induced growth arrest in G2/M phase to apoptotic cell death. |
Brentuximab vedotin (cAC10-vcMMAE) (10-120 mg/kg; i.p. for 3 weeks) the maximum tolerated dose (MTD) is between 30 and 40 mg/kg[2].
Brentuximab vedotin (cAC10-vcMMAE) (0.3, 1 mg/kg; flanks injection; every 4 days for a total of 4 doses 1 mg/kg) induces tumor CD30 regression[2].
| Animal Model: | SCID mice[2] |
| Dosage: | 10 to 120 mg/kg |
| Administration: | Intravenous injection; 10 to 120 mg/kg; for 3 weeks |
| Result: | Showed an maximum tolerated dose between 30 and 40 mg/kg. |
| Animal Model: | SCID mice[2] |
| Dosage: | 0.3 and 1 mg/kg |
| Administration: | Flanks injection; 1 mg/kg every 4 days for a total of 4 doses; 0.3 mg/kg every 4 days for a total of 4 doses |
| Result: | Induced complete and durable tumor regression, but 0.3 mg/kg provided lower therapy than 1 mg/kg dose. |
[1]. Shea L, Mehta-Shah N. Brentuximab Vedotin in the Treatment of Peripheral T Cell Lymphoma and Cutaneous T Cell Lymphoma. Curr Hematol Malig Rep. 2020 Feb;15(1):9-19.
[2]. Francisco JA, et al. cAC10-vcMMAE, an anti-CD30-monomethyl auristatin E conjugate with potent and selective antitumor activity. Blood. 2003 Aug 15;102(4):1458-65.
| Cas No. | 914088-09-8 | SDF | Download SDF |
| 别名 | 维布妥昔单抗；本妥昔单抗 | ||
| 分子式 | 分子量 | ||
| 溶解度 | 储存条件 | Store at 2-8°C,protect from light | |
| 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。 |
||
| 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。
The ECHELON-2 Trial: 5-year results of a randomized, phase III study of Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma
Ann Oncol 2022 Mar;33(3):288-298.PMID:34921960DOI:10.1016/j.annonc.2021.12.002.
Background: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that Brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. Patients and methods: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. Results: A total of 452 patients were randomized (1 : 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received Brentuximab vedotin, the objective response rate was 59% with Brentuximab vedotin retreatment after A+CHP and 50% with subsequent Brentuximab vedotin after CHOP. Conclusions: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.
Overall Survival with Brentuximab vedotin in Stage III or IV Hodgkin's Lymphoma
N Engl J Med 2022 Jul 28;387(4):310-320.PMID:35830649DOI:10.1056/NEJMoa2206125.
Background: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with Brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available. Methods: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed. Results: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up. Conclusions: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).
Brentuximab vedotin in T-cell lymphoma
Expert Rev Hematol 2019 Jan;12(1):5-19.PMID:30526166DOI:10.1080/17474086.2019.1558399.
Brentuximab vedotin is an antibody-drug conjugate, which combines a CD30 monoclonal antibody with the microtubule-disrupting agent monomethylauristatin E. The utility of Brentuximab vedotin has been explored in a number of diseases, with a recent focus on T-cell lymphoma, particularly systemic anaplastic large-cell lymphoma (sALCL) and cutaneous T-cell lymphoma (CTCL), as well as other peripheral T-cell lymphoma (PTCL) histologies. Areas covered: This review surveys current data on the efficacy of Brentuximab vedotin in T-cell lymphoma, as well as embedding it in a therapeutic context by reviewing potential competitor agents in the clinic. Data are drawn from published literature, with a focus on clinical trial data rather than preclinical studies or case reports. Expert opinion: Brentuximab vedotin has a clear clinical benefit in CTCL and sALCL, and can achieve durable responses in a number of patients. Toxicities, particularly peripheral neuropathy, may limit treatment in some patients; however, the agent is generally well tolerated. In this context, Brentuximab vedotin has been globally approved for use in sALCL and certain CTCL subtypes, however, further information is required to enhance our understanding of when and in whom to best employ this agent, as well as exploring rational combinations to augment responses.
Pembrolizumab versus Brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma (KEYNOTE-204): an interim analysis of a multicentre, randomised, open-label, phase 3 study
Lancet Oncol 2021 Apr;22(4):512-524.PMID:33721562DOI:10.1016/S1470-2045(21)00005-X.
Background: PD-1 blockade via pembrolizumab monotherapy has shown antitumour activity and toxicity in patients with relapsed or refractory classical Hodgkin lymphoma. Here, we present interim analyses from the KEYNOTE-204 study evaluating pembrolizumab versus Brentuximab vedotin for relapsed or refractory classical Hodgkin lymphoma. Methods: In this randomised, open-label, phase 3 study, patients aged 18 years or older with relapsed or refractory classical Hodgkin lymphoma with measurable disease and an Eastern Cooperative Oncology Group performance status of 0 or 1 who were ineligible for or had relapsed after autologous haematopoietic stem-cell transplantation (HSCT) were enrolled at 78 hospitals and cancer centres in 20 countries and territories. Patients were randomly assigned (1:1) with an interactive voice response system to pembrolizumab 200 mg intravenously every 3 weeks or Brentuximab vedotin 1·8 mg/kg intravenously every 3 weeks. Randomisation was stratified by previous autologous HSCT and status after front-line therapy. Results from the second interim analysis are presented here, with a database cutoff of Jan 16, 2020. The dual primary endpoints assessed in the intention-to-treat population were progression-free survival as assessed by blinded independent central review, and overall survival (not analysed at this interim analysis). Safety was assessed in all patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, NCT02684292. Recruitment for this trial is closed. Findings: Between July 8, 2016, and July 13, 2018, 151 patients were randomly assigned to pembrolizumab and 153 to Brentuximab vedotin. After a median time from randomisation to data cutoff of 25·7 months (IQR 23·4-33·0), median progression-free survival was 13·2 months (95% CI 10·9-19·4) for pembrolizumab versus 8·3 months (5·7-8·8) for Brentuximab vedotin (hazard ratio 0·65 [95% CI 0·48-0·88]; p=0·0027). The most common grade 3-5 treatment-related adverse events were pneumonitis (six [4%] of 148 patients in the pembrolizumab group vs one [1%] of 152 patients in the Brentuximab vedotin group), neutropenia (three [2%] vs 11 [7%]), decreased neutrophil count (one [1%] vs seven [5%]), and peripheral neuropathy (one [1%] vs five [3%]). Serious treatment-related adverse events occurred in 24 (16%) of 148 patients receiving pembrolizumab and 16 (11%) of 152 patients receiving Brentuximab vedotin. One treatment-related death due to pneumonia occurred in the pembrolizumab group. Interpretation: Pembrolizumab showed statistically significant and clinically meaningful improvement in progression-free survival compared with Brentuximab vedotin, with safety consistent with previous reports. These data support pembrolizumab as the preferred treatment option for patients with relapsed or refractory classical Hodgkin lymphoma who have relapsed post-autologous HSCT or are ineligible for autologous HSCT. Funding: Merck Sharp & Dohme Corp (a subsidiary of Merck & Co, Inc, Kenilworth, NJ, USA).
Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results
Blood 2021 Aug 12;138(6):427-438.PMID:33827139DOI:10.1182/blood.2020009178.
This phase 1-2 study evaluated Brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.