The U.S. Food and Drug Administration (FDA) has given Denovo Biopharma the green light to advance its investigational drug DB102 into a Phase 3 clinical trial for diffuse large B-cell lymphoma (DLBCL) patients.
The FDA granted Denovo’s Investigational New Drug application (IND) for DB102, clearing the way for the trial, called ENGINE (NCT03263026). The clinical trial has also been cleared by the China Food and Drug Administration (CFDA).
Denovo has acquired worldwide rights for DB102 (enzastaurin), which was originally developed by Eli Lilly. DB102 is a small molecule inhibitor of the PKC beta and AKT pathways, which are key for the survival, proliferation, and differentiation of several cancer types. In DLBCL, high levels of PKC beta are associated with poorer outcomes.
While the drug seemed promising for DLBCL, results from the PRELUDE Phase 3 trial (NCT00332202) failed to demonstrate satisfactory efficacy among people with the disease.
But recently, Denovo developed a genetic biomarker platform, DGM1 (Denovo Genomic Marker 1), that identifies patients who may benefit the most from DB102 treatment. Patients treated with DB102 across multiple studies were found to live longer if they were DGM1-positive, compared to those negative for the biomarker.
In particular, DB102 increased the efficacy of the standard chemotherapy drug combination known as R-CHOP in high-risk DLBCL patients who were positive for DGM-1.
These findings provided support for an IND application submission in the U.S. and China, and the design of the pivotal Phase 3 ENGINE study.
The trial, expected to enroll 235 participants, is designed to evaluate DB102 plus R-CHOP, versus R-CHOP alone, as a first-line treatment for patients with high-risk DLBCL.
Its primary goal is to determine the overall survival in DGM1-positive patients. Secondary measures include overall survival in DGM1-negative patients and safety parameters. The researchers will also determine if urine color can be used as a predictor of efficacy.
“Despite advances in novel therapies being developed to treat lymphoma, high risk (IPI>=3) DLBCL remains an unmet medical need and there are barely any clinical trials that specifically target this group of patients as front-line therapy,” Dr. Wen Luo, CEO of Denovo, said in a press release.
“We are very pleased with the acceptance of our phase 3 trial in both US and China, as it allows us to evaluate this innovative biomarker guided treatment as a potential new option to treat high risk DLBCL patients who are seeking a more effective therapy,” Luo added.