Blueprint announces results of key clinical trials of RET precision therapy for lung cancer

Blueprint公布RET精准疗法肺癌关键性临床试验结果

2020-01-09 14:07:07 medcitynews

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Blueprint Medicines today announced that its highly selective RET inhibitor pralsetinib (BLU-667) has achieved positive top-line results in ARROW, a Phase 1/2 clinical study of RET fusion-positive non-small cell lung cancer (NSCLC) patients . Blueprint Medicines has begun submitting a rolling NDA for this indication to the US FDA and is expected to complete its submission in the first quarter of this year. In addition, Blueprint Medicines plans to submit another new drug application for pralsetinib in the second quarter of this year to treat patients with myeloid thyroid tumor (MTC) previously treated with too many kinase inhibitors. Public data shows that lung cancer is the malignant tumor with the highest morbidity and mortality in the world, of which about 80% -85% are NSCLC, and the incidence of RET fusion in non-small cell lung cancer is about 1% ~ 2%. In MTC, almost all hereditary and about 50% of patients with sporadic medullary thyroid cancer are associated with mutations in the RET gene. MTC is a type of thyroid cancer. It is a common endocrine malignant tumor. Its incidence has increased significantly in recent years, and there is currently no effective standard treatment plan approved in China. In response to this clinical need, the Blueprint Medicines research team designed and developed an oral, potent, highly selective RET inhibitor pralsetinib that targets mutations in the RET gene based on its proprietary compound library. Public information shows that pralsetinib has consistently shown sub-nanomolar levels of efficacy against the most common RET gene fusions, activation mutations, and drug-resistant mutations in preclinical studies. And the drug's selectivity for RET is significantly improved compared to approved multikinase inhibitors. Among them, the activity on RET was increased by more than 80 times compared with VEGFR2. Cornerstone Pharmaceuticals obtained exclusive development and commercialization licenses for pralsetinib in mainland China, Hong Kong, Macau and Taiwan in June 2018. Currently, pralsetinib has obtained a number of regulatory qualifications. In April 2018, it was granted orphan drug status by the FDA to treat NSCLC patients with RET rearrangement. In February last year, the FDA granted a breakthrough therapy designation for patients with RET mutant MTC who require systemic treatment and no alternative treatment options. Last May, the FDA was granted another breakthrough therapy designation for patients with RET fusion-positive NSCLC who failed platinum-based chemotherapy. Data from the Phase 1/2 ARROW trial as of November 18, 2019 showed that among 80 subgroups of RET fusion-positive NSCLC patients who had previously received platinum chemotherapy, pralsetinib treatment resulted in an objective response rate (ORR) of 61 %, And reduced tumors in 95% of patients, including 14% of patients with complete regression of the target tumor. In a subgroup of 26 newly treated patients, pralsetinib treatment resulted in an ORR of 73% of patients, of which 12% achieved complete response (CR), and tumors shrank in all patients. Details of the trial will be announced at a future medical conference. "As the clinical data of pralsetinib matures, we also have data on the antitumor activity of pralsetinib in patients with brain metastases. We believe that pralsetinib has the potential to treat patients with RET fusion-positive NSCLC, including newly diagnosed metastatic patients and unresectable "Advanced patients," said Andy Boral, MD, Chief Medical Officer, Blueprint Medicines. "Now that we have obtained positive top-line data, we look forward to working with the US FDA to bring pralsetinib to patients in need as soon as possible.
今日,Blueprint Medicines公司宣布,其高选择性RET抑制剂pralsetinib(BLU-667),在治疗RET融合阳性非小细胞肺癌(NSCLC)患者的1/2期临床研究ARROW中,获得积极的顶线结果。Blueprint Medicines已开始向美国FDA递交这一适应症的滚动新药申请(rolling NDA),预计将在今年第一季度完成递交。此外,Blueprint Medicines还计划在今年第二季度递交pralsetinib的另一个新药申请,治疗先前接受过多激酶抑制剂治疗的甲状腺髓样瘤(MTC)患者。 公开数据显示,肺癌是全球发病率及死亡率最高的恶性肿瘤,其中约80%-85%为NSCLC,RET融合在非小细胞肺癌中的发生率约为1%~2%。而在MTC中,几乎所有遗传性和约50%的散发性甲状腺髓样癌患者均伴有RET基因突变。MTC是甲状腺癌的一种,是常见的内分泌恶性肿瘤,近几年其发病率显着上升,且中国目前尚无有效的获批标准治疗方案。 针对这一临床需求,Blueprint Medicines研究团队依据其专有化合物文库,设计并开发了靶向RET基因突变的口服,强效,高选择性的RET抑制剂pralsetinib。公开资料显示,在临床前研究中,pralsetinib针对最常见RET基因融合、激活突变和耐药突变始终表现出亚纳摩尔水平的效力。而且该药对RET的选择性与已批准的多激酶抑制剂相比有显着提高。其中,对RET的活性与VEGFR2相比提高了超过80倍。基石药业已于2018年6月获得了pralsetinib在中国大陆、香港、澳门和台湾地区的独家开发和商业化授权。 目前,pralsetinib已获得多个监管上的资格认定。2018年4月,它获得美国FDA授予的孤儿药资格,治疗RET重排的NSCLC患者。去年2月,获得FDA授予的突破性疗法认定,用于需系统治疗且无替代治疗方案的RET突变MTC患者。去年5月,获得FDA授予治疗经含铂化疗失败的RET融合阳性NSCLC患者的另一项突破性疗法认定。 截至2019年11月18日的1/2期ARROW试验数据显示,在80名先前接受过铂类化疗的RET融合阳性NSCLC患者亚组中,pralsetinib的治疗使患者的客观缓解率(ORR)达到61%,并且使95%的患者肿瘤缩小,其中包括14%目标肿瘤完全消退的患者。在含有26名初治患者的亚组中,pralsetinib的治疗使患者的ORR达到73%,其中12%的患者获得了完全缓解(CR),此外,所有患者的肿瘤均有缩小。该试验的详细数据将在未来的医学会议上公布。 “随着pralsetinib的临床数据日趋成熟,我们也得到了pralsetinib对脑转移瘤患者的抗肿瘤活性数据。我们认为,pralsetinib有潜力治疗RET融合阳性NSCLC患者,包括新诊断的转移性患者和不可切除的晚期患者,”Blueprint Medicines首席医学官Andy Boral医学博士说:“现在,我们已获得了积极的顶线数据,我们期待与美国FDA的下一步合作,尽快把pralsetinib带给有需要的患者。“

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