Signature program: a platform of basket trials
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Eric D. Slosberg1,10,*, Barinder P. Kang1,*, Julio Peguero2, Matthew Taylor3, Todd M. Bauer4, Donald A. Berry5,6, Fadi Braiteh7, Alexander Spira8, Funda Meric-Bernstam5, Steven Stein9, Sarina A. Piha-Paul5 and August Salvado1
1Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA
2Oncology Consultants PA, Houston, TX, USA
3Oregon Health and Science University, Portland, OR, USA
4Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, TN, USA
5The University of Texas MD Anderson Cancer Center, Houston, TX, USA
6Berry Consultants, Austin, TX, USA
7US Oncology Research and Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA
8Virginia Cancer Specialists, Fairfax, VA, USA
9Incyte, Wilmington, DE, USA
10Current affiliation: Daiichi Sankyo, Inc, Basking Ridge, NJ, USA
*These authors have contributed equally to this work
Barinder P. Kang, email: email@example.com
Keywords: signature; clinical trial design; basket trial; mutations; tissue agnostic
Received: September 30, 2017 Accepted: March 21, 2018 Published: April 20, 2018
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 PIK3CA, RAS, p16, and PTEN. 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.
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