什么是胃肠道间质瘤( gastrointestinal stromal tumor, GIST)?

GIST是胃肠道系统(包括胃、小肠和大肠)最常见的肉瘤,其特点为胃肠道组织中产生异常细胞。约5%的GIST患者具有PDGFRA的基因缺陷(已知的有D842V),并导致对现有批准的药物产生原发性耐药性。目前,尚无任何靶向治疗被批准用于治疗PDGFR突变型(D842V)GIST患者。

临床试验结果证明了crenolanib在PDGFRA D842V突变型GIST患者中的临床安全性和有效性。

血小板衍生生长因子受体(PDGFR) 概述

PDGFR基因异常(包括突变、缺失和扩增)在癌症中的发生率约为30%。PDGFR突变频率在10%以上的肿瘤包括GIST、胶质母细胞瘤、肺癌、黑素瘤、膀胱癌、前列腺癌、结肠直肠癌和卵巢癌等

 

ARO-021:Crenolanib联合化疗用于新诊断AML的研究

  • 本研究是在携带PDGFRA基因特异性突变(D842V)的晚期或转移性胃肠道间质瘤患者中进行的Crenolanib III期临床试验。
  • 本研究目前正在美国和欧洲的多个中心招募患者。
  • 本研究旨在评估,与安慰剂相比,Crenolanib能否安全有效地延长患者无疾病进展的时间。

有关该研究的更多信息,请联系参与研究的医院或访问 clinicaltrials.gov/ct2/show/NCT02847429

THERE ARE SEVERAL ATTRIBUTES THAT SET CRENOLANIB APART FROM OTHER THERAPEUTIC OPTIONS

  1. Crenolanib has shown benefit in PDGFRA-mutant GIST.
  2. Patients who progress after treatment with prior TKIs may still remain sensitive to crenolanib.
  3. Crenolanib has favorable pharmacokinetics and does not accumulate with repeated dosing.

Recent Peer-reviewed Publications

  1. Blay J-Y, Heinrich MC, Hohenberger P, et al. A randomized, double-blind, placebo-controlled, phase III study of crenolanib in advanced or metastatic GIST patients bearing a D842V mutation in PDGFRA: The CrenoGIST study. J Clin Oncol 2017; 35 (suppl; abstr TPS11080).
  2. von Mehren M, Tetzlaff ED, Macaraeg M, et al. Dose escalating study of crenolanib besylate in advanced GIST patients with PDGFRA D842V activating mutations. J Clin Oncol 2016; 34 (suppl; abstr 11010).
  3. Matro JM, Yu JQ, Heinrich MC, Ramachandran A, Ku N, Mehren Mv. Correlation of PET/CT and CT RECIST response in GIST patients with PDGFRA D842V gene mutations treated with crenolanib. J Clin Oncol 2014; 32:5s (suppl; abstr 10546).
  4. Heinrich MC, Griffith D, McKinley A, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumorsClin Cancer Res 2012; 18(16): 4375-84.
  5. Michael M, Vlahovic G, Khamly K, Pierce KJ, Guo F, Olszanski AJ. Phase Ib study of CP-868,596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor. Br J Cancer 2010; 103(10): 1554-61.
  6. Lewis NL, Lewis LD, Eder JP, et al. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868,596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers. J Clin Oncol 2009; 27(31): 5262-9.