打开APP

ASH2014:武田抗体偶联药物Adcetris大幅改善复发性系统间变大细胞淋巴瘤(sALCL)生存率

  1. Adcetris
  2. 抗体偶联药物
  3. 武田
  4. 淋巴瘤
  5. 系统性
  6. 间变性

来源:生物谷 2014-12-09 13:14

Adcetris是一种抗体偶联药物,靶向T细胞淋巴瘤CD30分子,关键II期研究中,Adcetris大幅改善了复发性系统间变大细胞淋巴瘤(sALCL)生存率,4年存活率高达64%。

2014年12月9日讯 /生物谷BIOON/ --2014年第56届美国血液学会年会(ASH)于12月6日-9日在美国旧金山举行。近日,西雅图遗传学公司(Seattle Genetics)和武田(Takeda)在会上公布了抗体偶联药物Adcetris一项关键性II期临床试验的数据。该研究在复发/难治系统性间变性大细胞淋巴瘤(sALCL)患者中开展,数据表明,平均随访46.3个月,估计的4年生存率为64%,平均无进展生存期(PFS)为20个月。

Adcetris是一种抗体药物偶联物(ADC),靶向于T细胞淋巴瘤(包括经典霍奇金淋巴瘤(cHL)和系统性间变性大细胞淋巴瘤(sALCL))高度表达的CD30分子。复发性T细胞淋巴瘤(cHL和sALCL)患者群体的历史结局一直不佳,平均总生存期(OS)为5.5个月,平均无进展生存期(PFS)为3.1个月。在复发性sALCL患者中开展的这项关键II期临床所取得的高达64%的4年生存率,很好地证明了Adcetris治疗复发性sALCL的有效性。

这些令人鼓舞的数据表明,Adcetris治疗复发性sALCL取得了可持续的长期缓解,支持了进一步评估Adcetris用于更早期的治疗。目前,西雅图遗传学公司和武田正在开展一项III期ECHELON-2研究调查Adcetris用于T细胞淋巴瘤的一线治疗。

关键II期临床研究:

该项关键单组II期研究在58例复发/难治系统性间变性大细胞淋巴瘤(sALCL)患者中开展,评估了Adcetris单药疗法的疗效和安全性。此外,该研究旨在确定缓解持续时间、无进展生存期(PFS)和总生存期(OS)。研究中,患者每3周接受一次静脉输注Adcetris(1.8mg/kg体重)共治疗16个疗程。正如此前所报道的,86%的患者实现客观缓解,其中59%(30例)实现完全缓解(CR),28%实现部分缓解(PR)。

从接受首次Adcetris治疗平均随访46.3个月,平均总生存期(OS)为55.1个月,预测的4年存活率为64%,平均无进展生存期(PFS)为20.0个月。实现完全缓解(CR)的38例患者中有19例(50%)在最后一次随访时仍保持缓解,平均总生存期(OS)和无进展生存期(PFS)尚未达到。16例实现完全缓解(CR)的患者接受了干细胞移植,OS和PFS数据也尚未达到。22例实现完全缓解(CR)但未接受干细胞移植的患者,平均无进展生存期(PFS)为39.4个月,平均总生存期(OS)尚未达到。未接受任何抗淋巴瘤治疗的8例CR患者仍保持缓解。

关于Adcetris:

Adcetris是一种抗体偶联药物(ADC),由靶向CD30蛋白的一种单克隆抗体和一种微管破坏剂(单甲基auristatin E,MMAE)通过一种蛋白酶敏感的交联剂偶联而成,该偶联技术为西雅图遗传学公司(Seattle Genetics)的专有技术。CD30蛋白是经典霍奇金淋巴瘤(HL)及系统性间变性大细胞淋巴瘤(sALCL)的明确标志物,而Auristatin E可通过抑制微管蛋白的聚合作用阻碍细胞分裂。Adcetris在血液中可稳定存在,在被CD30阳性肿瘤细胞内化后,可释放出MMAE。

Adcetris于2011年8月获FDA加速批准、于2012年10月获欧盟有条件批准、于2013年2月获加拿大批准。(生物谷Bioon.com)

英文原文:Seattle Genetics and Takeda Announce Four-Year Survival Data from ADCETRIS® (Brentuximab Vedotin) Pivotal Trial in Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma at ASH Annual Meeting

-Estimated Four-Year Survival Rate of 64 Percent-

-Half of Patients who Achieved Complete Remission Remain Disease-free-

Seattle Genetics, Inc. (SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502) today announced four-year overall survival (OS) data from the ADCETRIS (brentuximab vedotin) pivotal Phase 2 clinical trial in relapsed or refractory systemic anaplastic large cell lymphoma (ALCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma (HL) and systemic ALCL, a type of T-cell lymphoma. At a median follow up of 46.3 months, the estimated four-year survival rate was 64 percent. The data were presented at the 56th American Society of Hematology (ASH) Annual Meeting and Exposition taking place in San Francisco, CA, December 6-9, 2014.

“Historical outcomes for patients with relapsed T-cell lymphoma, including systemic ALCL have been poor, with a median overall survival of 5.5 months and a median progression-free survival of 3.1 months. The four-year survival data from the pivotal trial in systemic ALCL demonstrate ADCETRIS’ activity in the treatment of this disease, with an estimated four-year survival rate of 64 percent and a median progression-free survival of 20 months,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “These encouraging data show durable, long-term responses in the relapsed systemic ALCL treatment setting and support the evaluation of ADCETRIS in earlier lines of therapy, including in the ongoing Phase 3 ECHELON-2 clinical trial in frontline mature T-cell lymphoma.”

“The data estimate that more than 60 percent of the relapsed or refractory ALCL patients treated with ADCETRIS in this study are alive at four years, which may positively redefine outcome expectations in this difficult to treat cancer,” said Dirk Huebner, M.D., Senior Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “The fact that a third of all patients treated in the trial remain in complete remission with no evidence of disease after a median follow up of 46 months suggests the difference ADCETRIS can make in this disease.”

Four-Year Survival Data from an Ongoing Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma (Abstract #3095, poster presentation at 6:00 p.m. PT on Sunday, December 7, 2014 at the Moscone Center West Building, Level 1)

A pivotal, single-arm clinical trial was conducted in 58 relapsed or refractory systemic ALCL patients to assess the efficacy and safety of single-agent ADCETRIS. In addition, the trial was designed to determine duration of response, progression-free survival (PFS) and overall survival (OS). Patients received 1.8 milligrams per kilogram (mg/kg) of ADCETRIS administered through a 30-minute intravenous infusion every three weeks for up to 16 cycles. As previously reported, 86 percent of patients on the trial achieved an objective response, including 59 percent with a complete response (CR) and 28 percent with a partial response (PR).

Data from long-term patient follow up in this pivotal trial will be highlighted by Barbara Pro, M.D., Thomas Jefferson University, and include:

After a median observation time of 46.3 months from the first dose of ADCETRIS, the median OS was 55.1 months and the estimated four-year OS was 64 percent.
The median PFS per investigator was 20.0 months.
Nineteen of 38 patients (50 percent) who achieved a CR on study per investigator assessment remained in remission at the time of last follow-up; for all patients who achieved a CR, median OS and PFS had not yet been reached.
For the 16 CR patients who received a consolidative transplant (either allogeneic or autologous stem cell transplant), neither median PFS nor OS had been reached.
For the 22 CR patients who did not receive a consolidative transplant, median PFS was 39.4 months and median OS had not yet been reached. Eight CR patients remained in remission without receipt of any subsequent anti-lymphoma therapy following ADCETRIS.
The most common adverse events of any grade were peripheral neuropathy (57 percent), nausea (40 percent), fatigue (38 percent), pyrexia (34 percent) and diarrhea (29 percent).
The most common Grade 3 or 4 adverse events occurring in at least five percent of patients were neutropenia (21 percent), peripheral neuropathy (17 percent), thrombocytopenia (14 percent), anemia (seven percent) and recurrent ALCL (five percent).
About ADCETRIS:

ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics’ proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream and release MMAE upon internalization into CD30-expressing tumor cells.

ADCETRIS for intravenous injection received accelerated approval from the U.S. Food and Drug Administration and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of ASCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in 45 countries. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda will be solely responsible for development costs.

版权声明 本网站所有注明“来源:生物谷”或“来源:bioon”的文字、图片和音视频资料,版权均属于生物谷网站所有。非经授权,任何媒体、网站或个人不得转载,否则将追究法律责任。取得书面授权转载时,须注明“来源:生物谷”。其它来源的文章系转载文章,本网所有转载文章系出于传递更多信息之目的,转载内容不代表本站立场。不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。

87%用户都在用生物谷APP 随时阅读、评论、分享交流 请扫描二维码下载->