NEW YORK – San Diego-based Denovo Biopharma on Thursday announced that it has fully enrolled a registrational Phase III trial evaluating its investigational agent enzastaurin as a treatment for patients with high-risk, diffuse large B-cell lymphoma with a biomarker called de novo genomic marker 1 (DGM1).
The clinical trial, dubbed ENGINE, is randomizing roughly 235 patients to receive either enzastaurin plus the standard-of-care chemotherapy R-CHOP or R-CHOP alone. As a primary endpoint, ENGINE is assessing overall survival among patients with DGM1-positive disease, though as a secondary endpoint, the investigators will also evaluate overall survival in the population of patients who do not possess the DGM1 biomarker. The safety of the combination will be evaluated as a secondary endpoint, and as an exploratory endpoint researchers will look into whether abnormal urine color can predict the treatment's efficacy.
Denovo acquired enzastaurin, an oral small molecule inhibitor of the PKC beta, PI3K, and AKT pathways, from Eli Lilly in 2014, after the drug did not achieve its primary endpoint in initial Phase III clinical trials. To repurpose the drug, Denovo set out to identify genomic biomarkers using samples from a subset of patients who responded well to enzastaurin. Through retrospective analysis, Denovo has shown the ability of this DGM1 biomarker to predict outcomes among patients with DLBCL treated with enzastaurin, and the company will now assess whether the same holds true in the Phase III, prospective, randomized clinical trial.
An initial data readout from the DLBCL trial is expected in mid-2021.
Going forward, Denovo is also planning to conduct a Phase III trial of enzastaurin in patients with glioblastoma multiforme.