广谱Her不可逆抑制剂 Poziotinib (HM781-36B) 2期试验中期结果
本帖最后由 hoshiino 于 2017-11-5 00:06 编辑老马的介绍：Pan-Her不可逆抑制剂NOV120101 (Poziotinib)(HM781-36B)
Spectrum Pharmaceuticals Highlights Poziotinib Data in Non-Small-Cell Lung Cancer (NSCLC) Presented at the 18th IASLC World Conference on Lung Cancer in Japan
· Poziotinib demonstrates evidence of significant antitumor activity in NSCLC patients with EGFR exon 20 insertion mutations, with interim data showing an Objective Response Rate of 73%.
· Evidence of central nervous system (CNS) activity in a patient with CNS metastasis and another with leptomeningeal disease (LMD).
· On October 18th at 8:30 a.m. EDT/5:30 a.m. PDT, the Company will hold a conference call with Dr. John Heymach, from The University of Texas MD Anderson Cancer Center to discuss the study results.
October 17, 2017 10:15 PM Eastern Daylight Time
HENDERSON, Nev.--(BUSINESS WIRE)--Spectrum Pharmaceuticals, Inc. (NasdaqGS: SPPI), a biotechnology company with fully integrated commercial and drug development operations with a primary focus in Hematology and Oncology, announced the oral presentation of interim data from a Phase 2 clinical study evaluating poziotinib in EGFR Exon 20 Mutant Non-Small-Cell Lung Cancer (NSCLC) by scientists from the MD Anderson Cancer Center which was presented in Yokohama, Japan, October 15-18, 2017. The Company will hold a conference call tomorrow, October 18th, at 8:30 a.m. EDT/5:30 a.m. PDT with Dr. John Heymach, M.D., Ph.D., Chairman, Professor, and David Bruton Junior Chair in Cancer Research, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, to discuss his study results.
“These data are remarkable for NSCLC patients with exon 20 insertion mutations,” said John Heymach, M.D., Ph.D., The University of Texas MD Anderson Cancer Center. “These patients currently have a poor prognosis, single-digit response rate on first generation tyrosine kinase inhibitors (TKI’s), and a PFS of about two months. What is truly noteworthy is that all 11 study patients who received poziotinib at a 16mg daily dose and have reached their first scan, have seen some level of tumor shrinkage. Interestingly, we have also seen evidence of CNS activity. Toxicities have included rash, diarrhea, paronychia, and mucositis consistent with those previously described for poziotinib and other TKI’s, which led to dose reduction in 55% of the patients. We believe that poziotinib specifically inhibits EGFR with exon 20 insertion mutations because it overcomes steric hindrance caused by exon 20 insertions, due to its smaller size and flexibility. To date poziotinib has shown promising results in patients with exon 20 insertion mutations and we are fortunate to be leading the efforts in the continuing development of this product.”
“We are greatly encouraged with the clinical data emerging from poziotinib and plan to pursue its clinical development expeditiously and aggressively,” said Rajesh C. Shrotriya, M.D., Chairman and Chief Executive Officer of Spectrum Pharmaceuticals. “In the near future, we plan to discuss the regulatory pathway for poziotinib with the FDA. At the same time, we are embarking upon an overall strategy for global clinical development and regulatory filings. With three promising drugs in late-stage development, Spectrum’s pipeline has never been as exciting and our prospects never as bright.”
客观缓解率达73%！肺癌新药2期临床结果积极
日前，Spectrum Pharmaceuticals公司宣布了poziotinib在治疗携带EGFR外显子20插入突变(exon 20 insertion mutation)的非小细胞肺癌(NSCLC)患者的临床2期试验的中期结果，表明患者的客观缓解率达到73％。结果公布在国际肺癌研究协会(International Association for the Study of Lung Cancer, IASLC) 第18届世界肺癌大会上。
NSCLC是最常见的肺癌种类，而包括HER1(EGFR)、 HER2 和HER4在内的HER家族的酪氨酸激酶受体是最易被靶向的致癌基因。在HER受体的突变体中，外显子20插入突变是非经典突变类型中的重要一员。市场上目前存在的EGFR酪氨酸激酶抑制剂对携带这种突变的NSCLC疗效并不明显，患者的客观缓解率（ORR）只有8％左右，无进展生存期（PFS）只有2个月。与此相比，携带HER经典突变的NSCLC对现有酪氨酸激酶抑制剂的客观缓解率超过60％。对于携带HER外显子20插入突变的NSCLC患者来说，他们急需新的治疗选择。
Poziotinib是一种创新口服广谱HER抑制剂。它能够不可逆转地阻断所有HER家族酪氨酸激酶受体的信号传递。对携带外显子20插入突变的HER受体来说，有临床前试验表明poziotinib对它们的抑制效果是现有酪氨酸激酶抑制剂的几十倍。目前poziotinib正在进行乳腺癌，肺癌，胃癌，头颈癌等适应症的多项临床研究。
这项在德克萨斯大学MD安德森癌症中心(University of Texas MD Anderson Cancer Center)进行的开放标签，单臂临床2期试验中，25名携带EGFR外显子20插入突变的NSCLC患者接受了poziotinib的治疗。截止到发布中期试验结果时，11名接受扫描检查的患者的肿瘤都有不同程度的缩小，其中有8名患者的肿瘤缩小程度超过30％，以此为标准得出的客观缓解率为73％。同时，研究人员发现一名患者体内的中枢神经系统转移瘤对药物也有所反应。
药物的毒副作用包括皮疹、腹泻、甲沟炎(paronychia)和粘膜炎(mucositis)。这些副作用与poziotinib的前期试验和其它酪氨酸激酶抑制剂的副作用相似。毒副作用导致在55％的患者中药物剂量下调。
“Poziotinib的临床数据让我们非常受到鼓舞，我们将迅速积极地推动它的临床开发进程，”Spectrum公司的主席兼首席执行官Rajesh C. Shrotriya博士说：“近期我们将与FDA讨论poziotinib的监管通道，同时也将启动全球性的临床开发和监管申请过程。”
参考资料：
Spectrum Pharmaceuticals Highlights Poziotinib Data in Non-Small-Cell Lung Cancer (NSCLC) Presented at the 18th IASLC World Conference on Lung Cancer in Japan
Spectrum Pharmaceuticals官网
新科技带来新希望 春华秋实mama 发表于 2017-11-13 17:42
新科技带来新希望
最近看到一位病友家781吃了三个月缓慢耐药，还是有效的，可能丰度太低了
http://www.yuaigongwu.com/forum.php?mod=viewthread&tid=51445 Cancer Res Treat. 2017 Jan; 49(1): 10–19.
Published online 2016 May 3. doi:10.4143/crt.2016.058
PMCID: PMC5266390
A Phase II Study of Poziotinib in Patients with Epidermal Growth Factor Receptor (EGFR)-Mutant Lung Adenocarcinoma Who Have Acquired Resistance to EGFR–Tyrosine Kinase Inhibitors
二期实验效果不理想，还是二代药，没有实际价值 longyangagent 发表于 2017-11-16 23:15
Cancer Res Treat. 2017 Jan; 49(1): 10–19.
Published online 2016 May 3. doi:10.4143/crt.2016.058
...
781的定位不是一代耐药之后用，而是一线治疗20插入突变
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