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, August Salvado

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)21383-21395
Number of pages13
JournalOncotarget
Volume9
Issue number30
DOIs
StatePublished - Apr 20 2018
Externally publishedYes

Keywords

  • Basket trial
  • Clinical trial design
  • Mutations
  • Signature
  • Tissue agnostic

ASJC Scopus subject areas

  • Oncology

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