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.