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辉瑞肺癌药dacomitinib 2项III期研究失败

  1. dacomitinib
  2. 辉瑞
  3. 非小细胞肺癌

来源:生物谷 2014-01-28 10:11

辉瑞实验性肺癌药物dacomitinib 2项III期研究失败,该药为Dacomitinib不可逆pan-HER(泛-人表皮生长因子受体)激酶抑制剂。

2014年1月28日讯 /生物谷BIOON/ --辉瑞(Pfizer)1月27日公布了实验性肺癌药物dacomitinib的2项III期研究的结果。ARCHER 1009研究在既往接受过至少一次化疗(二线/三线)的晚期非小细胞肺癌(NSCLC)患者中开展,研究结果表明,与EGFR抑制剂厄洛替尼(erlotinib)相比,dacomitinib未能显著改善疾病无进展生存期(PFS),未能达到研究的主要终点。

另一项研究BR 26,在既往经至少一次化疗和一种EGFR酪氨酸激酶抑制剂的标准疗法治疗失败的局部晚期或转移性非小细胞肺癌(NSCLC)患者中开展,研究结果表明,与安慰剂相比,dacomitinib未能显著延长总生存期(OS),未能达到研究的主要终点。

目前,另一项III期研究ARCHER 1050正在进行中。该项研究在既往未经治疗的EGFR突变晚期NSCLC患者中开展,将dacomitinib与吉非替尼(gefitinib)进行比对,研究的主要终点是疾病无进展生存期(PFS)。该项研究的数据预计将于2015年获得。

关于Dacomitinib

Dacomitinib为每日一次的口服、不可逆pan-HER(泛-人表皮生长因子受体)激酶抑制剂,通过共价结合至受体酪氨酸激酶结构域,并阻止自磷酸化(autophosphorylation),不可逆地抑制HER1/EGFR、HER2、HER4的激酶活性,从而抑制下游信号传导,导致肿瘤生长抑制及凋亡。(生物谷Bioon.com)

英文原文:Pfizer lung cancer drug fails in two large studies

An Ongoing, Third Phase 3 Trial is Evaluating Dacomitinib in First-Line in EGFR-Mutant NSCLC  

Monday, January 27, 2014 - 7:00am EST
Pfizer Inc. (NYSE:PFE) today announced top-line results from two randomized Phase 3 studies of the irreversible pan-HER kinase inhibitor dacomitinib in patients with advanced non-small cell lung cancer (NSCLC).
 
Both trials evaluated dacomitinib in populations of previously treated patients with advanced NSCLC.  The ARCHER 1009 trial, which included patients previously treated with chemotherapy (second/third line), did not meet its objective of demonstrating statistically significant improvement in progression-free survival (PFS) when compared with the EGFR inhibitor erlotinib.
 
Separately, the NCIC CTG BR.26 trial, which included patients with advanced NSCLC after standard therapy with both chemotherapy and an EGFR tyrosine kinase inhibitor had failed, did not meet its objective of prolonging overall survival (OS) versus placebo.
 
An ongoing, third Phase 3 trial, ARCHER 1050, is evaluating PFS of dacomitinib in a different patient population than was studied in ARCHER 1009 and BR26.  ARCHER 1050 compares dacomitinib versus gefitinib in treatment-naïve (without prior treatment) patients with EGFR-mutant advanced NSCLC.  The results are expected in 2015.
                                         
“While we are disappointed in the results, lung cancer is a complex disease, and the use of targeted agents to treat specific patient populations continues to evolve,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.  “We are analyzing the findings from both ARCHER 1009 and BR.26 to better understand the effects of dacomitinib in molecularly defined subgroups of patients with advanced NSCLC, including those with EGFR mutations.”
 
The ARCHER 1009 trial evaluated dacomitinib versus erlotinib in two co-primary populations of patients with advanced NSCLC previously treated with at least one chemotherapy regimen – all patients and patients with KRAS wild-type NSCLC.  The study did not demonstrate that dacomitinib improved PFS in either of the co-primary populations compared to erlotinib.
 
The BR.26 trial was a double-blind, placebo-controlled, randomized study evaluating dacomitinib in patients with locally advanced or metastatic NSCLC after prior treatment, which included at least one chemotherapy regimen and one EGFR inhibitor treatment regimen.  This study was designed, conducted and led by NCIC Clinical Trials Group (NCIC CTG).
 
“We are pleased to have had the opportunity to assess dacomitinib in the BR.26 trial,” said Dr. Peter Ellis, BR.26 Study Chair and Associate Professor in the Department of Oncology, McMaster University, and medical oncologist at the Juravinski Cancer Centre, Hamilton, Ontario, Canada.  “While we are disappointed that the trial did not meet its primary endpoint, we are supportive of Pfizer’s commitment to continue to evaluate dacomitinib in the ARCHER 1050 trial.”
 
In both studies, the adverse events observed for dacomitinib generally were consistent with its known adverse event profile.  Full efficacy and safety data from ARCHER 1009 and BR.26 will be submitted for presentation at an upcoming medical meeting.
 
About Dacomitinib
Dacomitinib is an oral, once-daily, irreversible pan-HER (pan-human epidermal growth factor receptor) kinase inhibitor.  Dacomitinib irreversibly inhibits the kinase activity of HER1/EGFR, HER2, and HER4 by binding covalently to the receptor tyrosine kinase domains and preventing autophosphorylation, thereby inhibiting downstream signaling and leading to tumor-growth inhibition and apoptosis.
 
Dacomitinib is an investigational compound and has not received regulatory approval in any country.
 
Pfizer has entered into a collaborative development agreement with SFJ Pharmaceuticals Group to conduct ARCHER 1050 across multiple sites in Asia (including Japan) and Europe.
 
About Non-Small Cell Lung Cancer
Worldwide, lung cancer is the leading cause of cancer death in both men and women.[i]  NSCLC accounts for about 85 percent of lung cancer cases and remains difficult to treat, particularly in the metastatic setting.[ii]  Approximately 75 percent of NSCLC patients are diagnosed late with metastatic, or advanced, disease where the five-year survival rate is only 5 percent.

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