Novel agents with different molecular targets continue to emerge for B-cell malignancies, providing fertile ground to study combinations with potentially complementary mechanisms of action. This phase 1 trial evaluates the efficacy and safety of the triplet combination of the novel anti-CD20 agent ublituximab in combination with the PI3Kδ inhibitor TGR-1202 and the Bruton’s tyrosine kinase (BTK) inhibitor ibrutinib in patients with B-cell malignancies.
Eligible patients had chronic lymphocytic leukemia (CLL) or relapsed/refractory non-Hodgkin lymphoma (NHL). There was no limit to prior therapies, including those refractory to prior PI3Kδ or BTK inhibitors. A total of 38 patients were enrolled, of whom 29 were female. The median age was 65 years, and the median number of prior treatments was 3 (range, 0-6). Of the patients, 20 were diagnosed with CLL or small lymphocytic lymphoma (SLL); 18 patients were diagnosed with NHL, consisting of 6 with follicular lymphoma (FL), 6 with diffuse large B-cell lymphoma (DLBCL), 4 with mantle-cell lymphoma (MCL), and 2 with marginal zone lymphoma (MZL).
The maximum tolerated dose was not reached. The combination showed overall response rates of 100% for CLL/SLL (N = 19), MZL (N = 2), and MCL (N = 4); 80% for FL (N = 5); and 17% for DLBCL (N = 6). There was a median follow-up of 11.1 months (0.4-30+ months).
In terms of tolerability, the most common adverse events were diarrhea and fatigue (47% each), dizziness (37%), and insomnia and nausea (34% each). There were relatively few grade 3/4 adverse events; the only event >10% was neutropenia (18%).
The researchers concluded that the combination of ublituximab, TGR-1202, and ibrutinib was well-tolerated, with clinical activity observed across heavily pretreated and high-risk B-cell subgroups. Correlative studies are planned to further understand the potential synergy in different subgroups.
Nastoupil LJ, et al. ASCO Abstract 7511.
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