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It's a pleasure to be with you today. My name is Jeff Sharman. I'm the medical director of hematology research for US oncology. On behalf of the genuine clinical trial investigators and the patients enrolled in this study, it's my pleasure to provide you an update of the information that we presented here at the conference.
Patients with chronic lymphocytic leukemia have been very fortunate with the introduction of ibrutinib. This medication has transformed management for patients with this disease. Unfortunately, for patients with high risk features, such as 11q, 17p, or TP53 mutations, these patients experience the least durable benefit with ibrutinib monotherapy.
Ublituximab is a novel CD20 monoclonal antibody. It is a type-1 antibody that maintains compliment activation. It binds to a novel epitope on CD20 and it has been glycoengineered to enhance antibody-dependent cellular cytotoxicity.
In a previous clinical trial, we have demonstrated single agent activity in patients with disease refractory to rituximab and we have previously reported overall response rate of 88% amongst patients with relapsed CLL, who received an ibrutinib in combination ublituximab.
This clinical trial is a randomized phase three study in which half of patients receive ibrutinib monotherapy and half receive ublituximab in combination with ibrutinib. Patients were all found to have high risk molecular features and they were stratified according to lines of therapy. They were administered ublituximab on the schedule provided here.
This study was originally designed with co-primary endpoints of overall response and progression-free survival. However, due to challenges with enrollment, the protocol was modified to evaluate overall response rate exclusively as the primary endpoint such that it was no longer powered to detect changes in progression-free survival. Secondary endpoints are therefore progression-free survival, CR, MRD negativity, safety, and with the protocol modification, 120 patients were required.
Key eligibility criteria are shown here. And this is the disposition for patients: 100% of them had high risk features with approximately two-thirds having either 17p or TP53 mutation or both, one-third having 11q as their high risk feature. Three-quarters of patients remain on the study arm and a little over half remain on the standard are with the reasons for discontinuation shown here.
Baseline demographics is shown here, with the median age approximately 67 years, six and a half years from time of diagnosis to enrollment in therapy with baseline characteristics approximately equal between the two arms. With bulky disease being somewhat more common amongst those patients treated on the experimental arm.
Prior therapies are shown here, with 20% of patients having demonstrated rituximab refractory disease. Key safety findings are shown here, and I would highlight, the infusion reactions were more common to those patients who received ublituximab, as there were no infusions in who received ibrutinib monotherapy. Neutropenia was a little bit more common in patients on the experimental arm. However, rates of grade 3 for neutropenia were similar between the two study arms.
According to independent review committee overall response rate, the difference in overall response rate was 78% vs. 45%. CRs were only seen in the experimental arm and evaluation of MRD negativity occurred in 19% of patients were MRD negative on the experimental arm vs. 2% on the control arm. The impact on lymph node size was approximately similar between the two arms, slightly in favor of the combination therapy. And lymphocytosis was very different between the two arms, with patients treated with ibrutinib monotherapy having the typical lymphocytosis associated with ibrutinib monotherapy and this was abrogated by the addition of ublituximab. And this was true whether patients were considered rituximab refractory or not. Since the overall response was determined according to iwCLL 2008 criteria, which was part of the protocol. Yet, the response criteria have been updated over time to include partial response with lymphocytosis. We performed a secondary evaluation including those patients with PR-L. Amongst patients on the study, the overall response rate, including PRL, still favored those patients who received the experimental arm. The difference shown here - 83% to 59%, remaining statistically significant.
Progression-free survival is shown here and I would remind the audience that the study is not powered to detect a change in progression-free survival. There was hazard ratio in favor of the combination therapy, with a hazard ratio of .559 but the time of this evaluation is not statistically significant.
So in conclusion, the genuine study met its modified primary endpoint, demonstrating that ublituximab in combination with ibrutinib, yields superior overall response rate with greater depth of response. There is a trend towards favored progression-free survival, however, that is not statistically significant at the time of this analysis and, with the exception of infusion reactions, and ublituximab did not alter the safety profile of ibrutinib monotherapy. Thank you.