Slosberg Eric D, Kang Barinder P, Peguero Julio, Taylor Matthew, Bauer Todd M, Berry Donald A, Braiteh Fadi, Spira Alexander, Meric-Bernstam Funda, Stein Steven, Piha-Paul Sarina A, Salvado August
Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
Current affiliation: Daiichi Sankyo, Inc, Basking Ridge, NJ, USA.
Oncotarget. 2018 Apr 20;9(30):21383-21395. doi: 10.18632/oncotarget.25109.
Investigating targeted therapies can be challenging due to diverse tumor mutations and slow patient accrual for clinical studies. The Signature Program is a series of 8 phase 2, agent-specific basket protocols using a rapid study start-up approach involving no predetermined study sites. Each protocol evaluated 1 agent (buparlisib, dovitinib, binimetinib, encorafenib, sonidegib, BGJ398, ceritinib, or ribociclib) in patients with solid or hematologic malignancies and an actionable mutation. The primary endpoint of each study was the clinical benefit rate (ie, complete or partial response, or stable disease) at 16 weeks. A total of 192 individual sites were opened in the United States, with a median start-up time of 3.6 weeks. The most common tumor types among the 595 treated patients were colorectal (9.2%), non-small cell lung adenocarcinoma (9.1%), and ovarian (8.4%). Frequent genetic alterations were in , , , and . Overall, 30 partial or complete responses were observed with 6 compounds in 16 tumor types. The Signature Program presents a unique and successful approach for rapid signal finding across multiple tumors and allowed various agents to be evaluated in patients with rare alterations. Incorporating these program features in conventional studies could lead to improved trial efficiencies and patient outcomes.
由于肿瘤突变的多样性以及临床研究中患者入组缓慢，研究靶向治疗具有挑战性。Signature计划是一系列8项2期、针对特定药物的篮子试验方案，采用快速启动研究的方法，不涉及预先确定的研究地点。每个方案评估1种药物（布帕利西布、多韦替尼、比美替尼、恩考芬尼、索尼德吉、BGJ398、色瑞替尼或瑞博西尼）在实体或血液系统恶性肿瘤且有可操作突变的患者中的疗效。每项研究的主要终点是16周时的临床获益率（即完全缓解或部分缓解，或疾病稳定）。在美国共开设了192个独立研究点，启动时间中位数为3.6周。595例接受治疗的患者中最常见的肿瘤类型为结直肠癌（9.2%）、非小细胞肺腺癌（9.1%）和卵巢癌（8.4%）。常见的基因改变存在于……、……、……和……。总体而言，在16种肿瘤类型中，6种化合物观察到30例部分或完全缓解。Signature计划为跨多种肿瘤快速发现信号提供了一种独特且成功的方法，并允许在罕见改变的患者中评估各种药物。将这些计划特点纳入传统研究可能会提高试验效率和患者预后。
