Oncology Times

Update on Phase III Study of BTK Inhibitor for Diffuse Large B-Cell Lymphoma

An update on a phase III study (DBL3001) of ibrutinib in treatment-naïve diffuse large B-cell lymphoma (DLBCL), an aggressive form of non-Hodgkin lymphoma (NHL), was recently released.

Ibrutinib is a first-in-class Bruton's tyrosine kinase (BTK) inhibitor that has been available in the U.S. since 2013 and is FDA-approved for use in five B-cell blood cancers, as well as in chronic graft-versus-host disease for a total of eight FDA-approved indications.

 DLBCL is the most common form of NHL in adults, accounting for up to 40 percent of all cases worldwide. DLBCL can arise in lymph nodes or outside of the lymphatic system, in the gastrointestinal tract, testes, thyroid, skin, breast, bone, or brain. There are two main subtypes of DLBCL: germinal center B-cell-like (GCB) subtype and non-GCB subtype, which includes unspecific and activated B-cell-like (ABC). The disease occurs more commonly in the elderly and is slightly more prevalent in men.

DBL3001, a randomized, double-blind, placebo-controlled phase III study included 838 patients with newly diagnosed DLBCL, focusing on those with non-GCB/ABC subtypes. The study evaluated the addition of ibrutinib to a chemotherapy regimen consisting of five different agents used in combination—rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)—versus R-CHOP plus placebo. Participants were randomly assigned to receive either placebo plus R-CHOP or ibrutinib plus R-CHOP for 6-8 cycles, 21 days per cycle.

R-CHOP is the current standard of care in newly diagnosed DLBCL patients and provided as a first-line therapy for most patients today. The study was conducted in a subset of untreated DLBCL patients identified to have the non-GCB or ABC subtypes of this disease. Patients identified with non-GCB or ABC subtypes typically have poorer treatment outcomes and have greater unmet medical need.  

At conclusion of the study, data collected found that ibrutinib plus the chemotherapy regimen R-CHOP was not superior to R-CHOP alone, and that the study did not meet its primary endpoint of improving event-free survival in the targeted patient population. However, clinically meaningful improvements were observed in a patient sub-population that warrant further analysis. Full results from this study will be presented at an upcoming scientific conference and published in a peer-reviewed medical journal.

Ibrutinib is being studied alone and in combination with other treatments in several blood and solid tumor cancers and other serious illnesses. There are approximately 30 ongoing company-sponsored trials, 14 of which are in phase III, and more than 100 investigator-sponsored trials and external collaborations that are active around the world. To date, 100,000 patients around the world have been treated with ibrutinib in clinical practice and clinical trials.


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