Denovo Biopharma will start a global Phase 3 trial this year to assess its PKCβ inhibitor, DB102, as a first-line therapy for a subset of patients with diffuse large B-cell lymphoma (DLBCL).
The trial will use a biomarker that Denovo has developed — DGM1, for Denovo Genomic Marker 1 — to identify which lymphoma patients are likely to benefit from the therapy.
DB102, formerly known as Enzastaurin, is an oral, small-molecule inhibitor of the PKC beta and AKT protein-signaling pathways. Over-activation of the pathways is associated with poor outcomes in DLBCL patients.
A Phase 2 trial suggested that DB102 was a promising therapy for DLBCL patients, but it failed to achieve its primary treatment objective in a Phase 3 trial.
An extensive analysis using the DGM1 biomarker indicated that DB102 had substantially improved overall survival in a subset of patients in both the Phase 2 and Phase 3 trials. Those were patients the biomarker identified as DGM1-positive.
Denovo now wants to conduct a Phase 3 trial with those patients. The double-blind, placebo-controlled, global study will enroll patients in the United States and China.
“The successful discovery of the DGM1 biomarker is a major breakthrough for Denovo Biopharma, and has validated again the advantage of Denovo’s biomarker discovery platform,” Dr. Wen Luo, CEO of Denovo Biopharma, said in a news release. “Denovo’s unique precision medicine technology and business model allows us to unlock the hidden value in many of the drugs which have failed in late-stage trials. If the DGM1-driven DB102 clinical trial is successful as a first-line medication, it is expected to have a significant positive impact on patient outcomes and also to establish Enzastaurin as a significant new therapy for the treatment of DLBCL.”
Last year, Denovo opened a clinical center in Beijing. Its initial one is in San Diego.
“China will play a very important role in the biomarker-driven DB102 trial, and we have successfully submitted the IND [investigational new drug] application to the China FDA,” said Isabel Han, head of Denovo’s clinical operations in Beijing. “We are building an experienced clinical team to support all Denovo’s global clinical trials.”