ENGINE: A Phase III randomized placebo controlled study of enzastaurin/R-CHOP as frontline therapy in high-risk diffuse large B-cell lymphoma patients with the genomic biomarker DGM1

Grzegorz S. Nowakowski, Jun Zhu, Qingyuan Zhang, Joshua Brody, Xiuhua Sun, Joseph Maly, Yuqin Song, Syed Rizvi, Yongping Song, Frederick Lansigan, Hongmei Jing, Junning Cao, Jennifer K. Lue, Wen Luo, Lei Zhang, Ling Li, Isabel Han, Joan Sun, Manoj Jivani, Young LiuThomas Heineman, Stephen D. Smith

Research output: Contribution to journalArticle

Abstract

While combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) cures most patients with diffuse large B-cell lymphoma (DLBCL), those with high-risk international prognostic index disease have inferior survival. Enzastaurin as a potent inhibitor of PKC-β and PI3K/AKT pathway suppressor has been tested in many clinical trials including two key studies in DLBCL: Phase III maintenance study (Preventing Relapse in Lymphoma Using Daily Enzastaurin [PRELUDE]) and a first-line Phase II study (S028). DNA extracted from PRELUDE patients' blood samples was retrospectively genotyped identifying a novel genetic biomarker, DGM1 that showed high correlation with response to enzastaurin. A similar finding observed in the S028 study suggested that addition of enzastaurin to R-CHOP may significantly improve outcomes as frontline therapy for high-risk DGM1 positive DLBCL patients. ENGINE is a global, multicenter, placebo-controlled and randomized study to compare the effect of R-CHOP/enzastaurin as frontline treatment in high-risk DLBCL patients. The primary end point for this study is overall survival in patients who are DGM1 positive. Clinical Trial Registration Identifier: NCT0326302.

Original languageEnglish (US)
Pages (from-to)991-999
Number of pages9
JournalFuture Oncology
Volume16
Issue number15
DOIs
StatePublished - May 2020

Keywords

  • DGM1
  • Enzastaurin
  • Lymphoma
  • Personalized chemotherapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Nowakowski, G. S., Zhu, J., Zhang, Q., Brody, J., Sun, X., Maly, J., Song, Y., Rizvi, S., Song, Y., Lansigan, F., Jing, H., Cao, J., Lue, J. K., Luo, W., Zhang, L., Li, L., Han, I., Sun, J., Jivani, M., ... Smith, S. D. (2020). ENGINE: A Phase III randomized placebo controlled study of enzastaurin/R-CHOP as frontline therapy in high-risk diffuse large B-cell lymphoma patients with the genomic biomarker DGM1. Future Oncology, 16(15), 991-999. https://doi.org/10.2217/fon-2020-0176