诺华皮肤癌新药sonidegib III期研究成功

【诺华皮肤癌新药sonidegib III期研究成功】诺华2月19日宣布在研口服选择性SMO抑制剂LDE225 (sonidegib)一项关键III期研究到达主要终点。晚期基底细胞癌患者经过6个月的治疗，取得具有临床显著意义的肿瘤学应答，部分患者肿瘤完全消失。具体数据待公布。基底细胞癌是黑色素瘤之外的常见皮肤癌，约占80%

关键词： 诺华 LDE225 sonidegib 基底细胞癌



2014年2月20日讯 /生物谷BIOON/ --诺华（Novartis）2月19日宣布，有关实验性抗癌药LDE225（sonidegib）的一项关键性II期研究BOLT达到了客观缓解率（objective response rate，ORR）的主要终点。客观缓解包括完全缓解（临床上肿瘤显著缓解，无疾病）和部分缓解（临床上肿瘤显著缩小）。该项研究的完整数据将提交至未来的科学会议。

基底细胞癌（basal cell carcinoma）是一种最常见形式的皮肤癌，占非黑色素瘤皮肤癌的80%以上，在全球范围内，该病的发病率每年上升10%。

BOLT是一项随机、双盲II期研究，旨在评估2种口服剂量的LDE225（200mg，800mg）用于局部晚期或转移性基底细胞癌患者治疗的疗效和安全性。该研究的主要终点为，接受LDE225治疗的6个月内，取得客观缓解率的患者比例。该研究的关键次要终点包括评估肿瘤缓解的持续时间及完全缓解率，其他次要终点包括无进展生存期、总生存期及取得肿瘤缓解的时间。

关于LDE225：

LDE225是一种口服、选择性Smoothened蛋白（SMO）抑制剂，目前正调查用于多种癌症的治疗，包括骨髓纤维化、白血病及实体瘤。Smoothened蛋白调控Hedgehog（Hh）信号通路，该通路在干细胞维持及组织修复中发挥着关键作用。

英文原文：Novartis investigational compound LDE225 met primary endpoint in pivotal trial for patients with advanced basal cell carcinoma

Results show LDE225 achieved clinically significant tumor response including disappearance of the tumor in some patients within six months of treatment

Basal cell carcinoma accounts for more than 80% of non-melanoma skin cancers and can be highly disfiguring and life-threatening when advanced or metastatic[1],[2],[3]

Data will be presented at a future scientific meeting and discussed with regulatory authorities worldwide

Basel, February 19, 2014 - Novartis announced today that the pivotal trial of the investigational oral compound LDE225 (sonidegib) in advanced basal cell carcinoma met its primary endpoint of demonstrating an objective response rate among patients within six months of treatment. Objective response included complete response (clinically significant tumor response with complete absence of disease) and partial response (clinically significant tumor shrinkage)[4],[5],[6].

Basal cell carcinoma is the most common form of skin cancer, accounting for more than 80% of non-melanoma skin cancers, and can be highly disfiguring and life-threatening if it grows[1],[2],[3]. Worldwide incidence of basal cell carcinoma is rising by 10% each year due to factors such as an aging population and increased ultraviolet exposure[7]. Although basal cell carcinoma rarely metastasizes, once it does, it can be associated with significant morbidity[8].

"For people living with advanced basal cell carcinoma there are currently limited treatment options," said Alessandro Riva, President, Novartis Oncology ad interim and Global Head, Oncology Development and Medical Affairs. "These results demonstrate the potential for LDE225 to offer a treatment option for this patient population, and we look forward to sharing these data with regulatory authorities worldwide."

Full study results will be presented at a future scientific meeting.

About the Study
The Phase II, randomized, double-blind BOLT (Basal cell carcinoma Outcomes in LDE225 Trial) study was designed to assess the safety and efficacy of two oral dose levels of LDE225 (200 mg and 800 mg) in patients with locally advanced or metastatic basal cell carcinoma[4], which are subtypes of advanced basal cell carcinoma[9].

The primary endpoint was the proportion of patients achieving an objective response rate, defined as a confirmed complete response and partial response as their best overall response per modified RECIST criteria, within six months of starting treatment with LDE225[4]. Key secondary endpoints of the study included assessing the duration of tumor responseand the rate of complete response[4]. Other secondary endpoints included progression-free survival, time to tumor response and overall survival[4].

About LDE225
LDE225 (sonidegib) is an oral, investigational, selective smoothened inhibitor being studied in a variety of cancers[10],[11]. Smoothened (SMO) is a molecule that regulates the hedgehog (Hh) signaling pathway, which plays a critical role in stem cell maintenance and tissue repair[10],[12],[13]. LDE225 is currently in clinical development for a variety of diseases including myelofibrosis, leukemia and solid tumors[11].

Given that LDE225 is an investigational compound, the safety and efficacy profile has not yet been fully established. Access to this investigational compound is available only through carefully controlled and monitored clinical trials. These trials are designed to better understand the potential benefits and risks of the compound. Given the uncertainty of clinical trials, there is no guarantee that LDE225 will ever be commercially available anywhere in the world.

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