Oncotarget

Research Papers:

Signature program: a platform of basket trials

Eric D. Slosberg, Barinder P. Kang _, Julio Peguero, Matthew Taylor, Todd M. Bauer, Donald A. Berry, Fadi Braiteh, Alexander Spira, Funda Meric-Bernstam, Steven Stein, Sarina A. Piha-Paul and August Salvado

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Oncotarget. 2018; 9:21383-21395. https://doi.org/10.18632/oncotarget.25109

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Abstract

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

Correspondence to:

Barinder P. Kang, email: barinder.kang@novartis.com

Keywords: signature; clinical trial design; basket trial; mutations; tissue agnostic

Received: September 30, 2017    Accepted: March 21, 2018    Published: April 20, 2018

ABSTRACT

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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