We have seen durable responses as well, with the median time on therapy of 11 months or longer. We have also not seen an increase in toxicity with longer drug exposure. This appears to be a safe and highly effective combination.
Is there anything else you would like to note about these findings?
This is a phase I study with a small cohort of patients. What is notable about the study is we do have a meaningful duration of drug exposure. What we have learned from prior PI3K-delta inhibitors is that there are unique side effects, particularly colitis, transaminitis, pneumonitis or infection, that have impeded patients’ ability to stay on the drug. This may have a differentiated safety profile, and we have at least 80% of patients over 11 months of drug exposure with the PI3K-delta inhibitor TGR-1202. We have not seen the same rates of AEs associated with drugs such as idelalisib (Zydelig) or duvelisib.
Again, notable is the colitis rate of 3%. We did not have a significant rate of transaminitis. Now, there was a high rate of neutropenia of 18%, albeit that compares favorably with chemotherapy, particularly in a patient population that has [received] numerous therapies. The pneumonia rate of 11% seems to be favorable cross-comparison with other PI3K-delta inhibitors. We think that this may speak to the selectivity of the PI3k-delta inhibitor umbralisib. However, a longer follow-up and more patient exposure will be needed to be comfortable in that conclusion.
What are the next steps following these findings?
This is a very novel, interesting combination that may lead to deeper responses; the response does appear to be durable and the combination does appear to be safe with at least the 38 patients who were evaluable for safety. The next step for this combination is to examine if this should be available for all patients with B-cell lymphomas, or should it be specific to CLL—where we know that targeting the B-cell receptor signaling pathway may be more favorable.
Studies are planned or ongoing to identify a specific population where this novel combination may be expanded upon. We also feel that this PI3K-delta inhibitor (umbralisib), because it may have a differentiated safety profile, may be a favorable agent to combine with agents with the role of synergism.
- Nastoupil L, Lunning MA, Vose JM, et al. Tolerability and activity of chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib in patients with advanced CLL and NHL. J Clin Oncol 35, 2017 (suppl; abstr 7511).
- Nastoupil L, Lunning MA, Vose JM, et al. Chemo-free triplet combination of TGR-1202, ublituximab, and ibrutinib is well tolerated and highly active in patients with advanced CLL and NHL. In: Proceedings from the 2017 EHA Congress; June 22-25, 2017; Madrid, Spain. Abstract S772. learningcenter.ehaweb.org/eha/2017/22nd/182059/loretta.nastoupil.chemo-free.triplet.combination.of.tgr-1202.ublituximab.and.html.