Ibrutinib Combination Therapy for DLBCL Falls Short of Phase 3 Primary Endpoint

Ibrutinib (IMMBRUVICA) is a small molecule drug that works to block the protein, Bruton’s tyrosine kinase (BTK), which prevents the transmission of signals that cause B cells to mature and make antibodies, thus starving cancer cells and preventing them from multiplying and migrating.

Since 2013, ibrutinib has been available in the United States; it has won approval from the US Food and Drug Administration (FDA) for the treatment of 5 B-cell blood cancers, as well as in chronic graft-versus-host-disease, for a total of 8 approved indications.

The safety and effectiveness of the drug is currently being evaluated in a phase 3 trial looking at treatment naïve patients with diffuse large B-cell lymphoma (DLBCL), which is the most common type of non-Hodgkin lymphoma (NHL), a rare blood cancer.

The phase 3 trial, referred to as DBL3001, assessed ibrutinib in a subset of untreated DLBCL patients contain to have the non-germinal center B cell (GCB) or activated B-cell (ABC) subtypes of the disease. These patient populations are known to have poorer treatment outcomes, and thus, a greater unmet medical need.

For the trial, patients received ibrutinib in combination with a chemotherapy regimen comprised of 5 different agents—rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)—or R-CHOP plus placebo. Currently, R-CHOP is the standard of care for patients newly diagnosed with the cancer, and for most patients, it serves as first-line treatment.

The ibrutinib plus RCHOP combination therapy was not found to be more effective than R-CHOP treatment alone, and thus, the study did not meet its primary endpoint of improving event-free survival (EFS) in the targeted patient population. However, in a patient sub-population, clinically meaningful improvements were noted, and as such, analyzed further at a later date.

“We continue to believe that ibrutinib has great untapped potential as a cancer treatment alone or in combination. Together with our global partner Janssen, we are advancing our robust ibrutinib scientific development program and anticipate results from several studies in the future,” Thorsten Graef, MD, PhD, head of Clinical Development at Pharmacyclics LLC, an AbbVie company, said in a recent comment.

The full results of the study are set to publish in a peer-reviewed medical journal and will be presented at an upcoming scientific conference, according to AbbVie.

Another ibrutinib combination therapy is recently evaluated for the treatment of relapsed/refractory and treatment-naïve patients with Waldenström macroglobulinemia, another rare form of NHL, which is currently incurable. When combined with rituximab in the phase 3 iNNOVATE trial, the treatment resulted in an overall response rate of 92%.