2014年10月23日讯 /生物谷BIOON/ --勃林格殷格翰（BI）近日宣布，启动一项全球III期研究，调查实验性抗癌药物nintedanib用于晚期结直肠癌（CRC）的治疗。
结直肠癌是全球第三大常见癌症，每年增加140万新发病例。晚期结直肠癌患者的预后很差，确诊后5年存活率小于10%。nintedanib是一种口服三联血管激酶抑制剂，目前，勃林格正在多种实体瘤中评价nintedanib。在美国，FDA于今年10月批准nintedanib用于特发性肺纤维化（IPF）的治疗。
LUME-COLON-1是一项双盲、随机、安慰剂对照III期研究，在既往经标准化疗和生物制剂治疗后病情恶化的晚期结直肠癌（CRC）患者中开展，目的是评估nintedanib+最佳支持治疗（BSC）组合疗法相对于安慰剂+BSC的疗效和安全性。该项研究的启动，是基于在晚期结直肠癌I/II期临床中观察到的nintedanib早期疗效迹象。
LUME-COLON-1研究计划招募超过750例既往已接受治疗但病情恶化的晚期结直肠癌患者，将在全球150个网点开展。患者随机接受nintedanib（200mg，每天2次）+BSC组合疗法或安慰剂+BSC。最佳支持治疗（BSC）定义为每个研究者决定的最佳姑息治疗。该研究的复合主要终点为无进展生存期（PFS）和总生存期（OS），次要终点包括肿瘤客观缓解率（ORR）和疾病控制率（DCR）。
在欧盟，欧洲药品管理局（EMA）人用医药产品委员会（CHMP）已建议批准nintedanib联合多西他赛（docetaxel）用于既往经一线化疗治疗的局部晚期、转移性或局部复发性腺癌组织学非小细胞肺癌（NSCLC）患者的治疗。此外，勃林格已向EMA提交了nintedanib治疗特发性肺纤维化（IPF）的上市许可申请（MAA）。在美国，FDA已于今年10月批准Ofev（nintedanib）胶囊，作为一种口服药物，用于IPF的治疗。
关于Ofev（nintedanib）
Nintedanib是一种口服三联血管激酶抑制剂，可同时阻断3种生长因子受体：血管内皮生长因子受体（VEGFR 1-3）、血小板源性生长因子受体（PDGFR α和β）、成纤维细胞生长因子受体（FGFR 1-3）。所有这3种受体在血管生成和肿瘤生长过程中均发挥着重要作用。这些受体的阻断，可能导致血管生成的抑制，而血管生成在肿瘤生长中起着关键作用。
目前，勃林格殷格翰正在多种实体瘤中评价nintedanib，其中晚期非小细胞肺癌（NSCLC）、结直肠癌、卵巢癌已处于III期临床，间皮瘤、肾癌（肾细胞癌）、肝癌（肝细胞癌）处于II期临床。
英文原文：Boehringer Ingelheim initiates global Phase III study investigating nintedanib* in patients with colorectal cancer refractory to standard treatments
• LUME-COLON 1 will evaluate the efficacy and safety of nintedanib* in specific patients with colorectal cancer, whose disease has progressed on previous treatment1
• The study builds on the early efficacy sign observed in previous studies with nintedanib* in colorectal and lung cancer2
• The study will enrol more than 750 patients at 150 sites worldwide, with locations in U.S., Europe and Asia
Ingelheim, Germany, 21 October 2014 – Boehringer Ingelheim today announced the enrolment of the first patient in a new global Phase III study in patients with advanced colorectal cancer (CRC). Colorectal cancer is the third most common cancer in the world, with nearly 1.4 million new cases diagnosed each year.3 Prognosis is poor for patients with advanced CRC with fewer than 10% surviving for more than five years after diagnosis.3
LUME-COLON 1 [ClinicalTrials.gov identifier: NCT02149108] is a double-blind, randomised, placebo-controlled study designed to evaluate the efficacy and safety of nintedanib* plus best supportive care (BSC), versus placebo plus BSC, after previous treatment with standard chemotherapy and biological agents.1 This new study builds on the early efficacy signs observed with nintedanib* in CRC during Phase I/II trials.4,5
“There is a significant need to improve treatment options for patients with advanced colorectal cancer and Boehringer Ingelheim is proud to conduct further research into this disease area. The initiation of LUME-COLON 1 reinforces our ongoing commitment to driving innovation in oncology research,” said Professor Klaus Dugi, Chief Medical Officer, Boehringer Ingelheim.
LUME-COLON 1 plans to enrol more than 750 patients with CRC, whose disease has progressed on previous treatment and will be conducted at 150 sites worldwide, with locations in the U.S., Europe and Asia, amongst others. Patients will receive either nintedanib* 200mg twice daily plus BSC, or matching placebo plus BSC. BSC is defined as the best palliative care per investigator decision. The co-primary endpoints will be progression-free survival (PFS), evaluated by blinded review and overall survival (OS).1 Secondary endpoints are objective tumour response rate and disease control rate.1
In the EU, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion for the approval of nintedanib* in combination with docetaxel for the treatment of adult patients with locally advanced, metastatic or locally recurrent NSCLC of adenocarcinoma tumour histology after first line chemotherapy.
Another EU marketing authorisation application (MAA), has been submitted for nintedanib* in the treatment of idiopathic pulmonary fibrosis (IPF). In the U.S., the Food and Drug Administration (FDA) has approved nintedanib* capsules under the brand name OFEV™ for oral use for the treatment of IPF.
About nintedanib*
Nintedanib* is an oral triple angiokinase inhibitor which simultaneously inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptors (PDGFR) and fibroblast growth factor receptor (FGFR) signalling pathways, the three receptors crucially involved in angiogenesis and tumour growth.6 Growing scientific evidence shows that these three different angiokinase receptors play an important role not only in angiogenesis but also in tumour growth and metastasis.7,8
Nintedanib* is currently being investigated in patients with various solid tumours including Phase III studies in advanced NSCLC2, colon cancer (colorectal cancer refractory to standard treatment)9 and ovarian cancer10, and also in Phase II studies in mesothelioma11, kidney cancer (renal cell carcinoma)12 and liver cancer (hepatic cell carcinoma)13.
About Colorectal Cancer
Colorectal cancer is a cancer in the colon or rectum (parts of the large intestine). Like other cancers, colorectal cancer starts in a small area but can spread to other parts of the body to form metastatic tumours.14 Symptoms of colorectal cancer typically include rectal bleeding and anaemia which are sometimes associated with weight loss and changes in bowel habits.15 Some colorectal cancers occur due to lifestyle, increasing age or underlying genetic causes.16 Colorectal cancer is the third most common cancer in the world, with nearly 1.4 million new cases diagnosed each year. It is predicted that this number will increase to 2.4 million cases each year by 2035.17