Ibrutinib/R-CHOP Fails to Meet Primary Endpoint in Phase III DLBCL Trial

A phase III trial combining ibrutinib with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) failed to meet its primary endpoint as a frontline treatment for patients with newly diagnosed diffuse large B-cell lymphoma, according to results detailed in a press release issued by ibrutinib’s manufacturer, AbbVie.

In the DBL3001 trial, the combination of ibrutinib and R-CHOP was not superior to treatment with R-CHOP alone. Nonetheless, in the press release, the manufacturer noted that “clinically meaningful improvements were observed in a patient subpopulation that warrant further analysis.”

No details on what improvements or patient population are given in the release. Full results from the study will be presented at an upcoming scientific conference and published in a peer-reviewed medical journal, according to the release.

"Since its first US FDA approval in 2013, IMBRUVICA has redefined standard of care in many different blood cancers-several of which had little to no treatment options available to patients before," said Thorsten Graef, MD, PhD, head of clinical development at Pharmacyclics LLC, an AbbVie company.

"These medical achievements reflect our objective of focusing research where there is great unmet patient need and understanding that the nature of research is such that some studies succeed and others do not. We continue to believe that ibrutinib has great untapped potential as a cancer treatment alone or in combination.”

The current standard of care for patients with newly diagnosed DLBCL is R-CHOP. The DBL3001 study was designed to evaluate if adding the Bruton tyrosine kinase inhibitor ibrutinib to R-CHOP provided any additional benefit.

The phase III study included 838 patients with newly diagnosed DLBCL who were randomly assigned to treatment with placebo plus R-CHOP or ibrutinib plus R-CHOP for 6 to 8 cycles, with 21 days per cycle. Included patients had the non–germinal center B-cell (GCB) or activated B-cell (ABC) subtypes of the disease. The two regimens were found to be equivalent in terms of the event-free survival endpoint in the targeted population.

Ibrutinib also recently failed to meet the primary endpoint of overall response in a phase II trial of patients with chemoimmunotherapy-relapsed or -refractory follicular lymphoma. Again, in this study, the researchers said that data from secondary endpoints “suggest benefits of this therapy in some patients.”

Ibrutinib is currently approved by the US Food and Drug Administration for patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, Waldenstrom macroglobulinemia, previously treated mantle cell lymphoma, previously treated marginal zone lymphoma, and previously treated chronic graft-vs-host disease.