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 Oncol. 2020 May;16(15):991-999. doi: 10.2217/fon-2020-0176. Epub 2020 Apr 6.


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: NCT03263026.

Keywords: DGM1; enzastaurin; lymphoma; personalized chemotherapy.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Biomarkers, Tumor* / genetics
  • Clinical Trials, Phase III as Topic
  • Cyclophosphamide / adverse effects
  • Cyclophosphamide / therapeutic use
  • Doxorubicin / adverse effects
  • Doxorubicin / therapeutic use
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Indoles / administration & dosage
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / mortality
  • Male
  • Prednisone / adverse effects
  • Prednisone / therapeutic use
  • Randomized Controlled Trials as Topic
  • Research Design
  • Rituximab / adverse effects
  • Rituximab / therapeutic use
  • Vincristine / adverse effects
  • Vincristine / therapeutic use


  • Biomarkers, Tumor
  • Cyclophosphamide
  • Doxorubicin
  • enzastaurin
  • Indoles
  • Prednisone
  • R-CHOP protocol
  • Rituximab
  • Vincristine

Associated data

  • ClinicalTrials.gov/NCT03263026