CONCORD, Mass.—Early December saw non-Hodgkin’s lymphoma (NHL) news from Alopexx Oncology LLC when it announced data from a Phase 1 trial of DI-Leu16-IL2, a recombinant antibody fusion protein (immunocytokine) composed of interleukin-2 and a CD20-targeting monoclonal antibody.
The CD20 antibody recognizes the same target on B cells as Rituxan and maintains the activities of both the antibody and cytokine components, but is also involved in tumor targeting, engagement of the immune system and induction of an anticancer vaccine effect. The results of the study were presented at the 58th annual American Society of Hematology (ASH) meeting in San Diego.
Twenty-two patients with relapsed or refractory B-cell CD20-positive lymphoma, in five dose cohorts, have been enrolled. Fifteen of 18 patients receiving two or more cycles of therapy had tumor regression or stabilization including three complete and two partial responses. The durations of response were over 12 months in many cases. The durability of those responses was maintained in patients months after stopping treatment, suggesting a vaccine effect had occurred. These study results are similar to a previous investigator-sponsored Phase 1 study conducted at the City of Hope by Dr. Andrew Raubitschek.
Overall, DI-Leu16-IL2 was well tolerated as outpatient therapy. Unlike normal IL-2 treatment, the most common toxicities encountered were a mild skin rash that resolved spontaneously. Subcutaneous dosing was employed in the study to deliver the drug directly into the lymphatic system, allowing for higher dosing and lower side effects than with IV infusion. In addition, the effective dose of DI-Leu16-IL2 was 100-200-fold lower than Rituxan. This suggests that by targeting the tumor microenvironment, an effective treatment can occur at a much lower dose and opens the door to future combination therapy with established drugs like immune checkpoint inhibitors.
“The findings to date are very encouraging and support our belief that DI-Leu16-IL2 has the potential to become an effective therapy in the treatment of refractory NHL either alone or in combination,” said Dr. Daniel Vlock, founder and CEO of Alopexx Enterprises.
CD20 is a protein frequently expressed on cancer cells associated with NHL. Preclinical studies have shown that DI-Leu16-IL2, which has activities of both the anti-CD20 antibody and cytokine components, targets the tumor cells, engages the immune system and has the potential to produce an anti-cancer vaccine effect. As a result of this vaccine-like effect, long-term anticancer activity should continue and future cancer cells could be destroyed even without the need for re-dosing.
“The fusion of the anti-CD20 antibody and the cytokine IL2 creates an effect that is far more powerful than administering those therapeutics individually or in combination,” explained Dr. Stephen Gillies, chief scientific officer of Alopexx Oncology. “In this therapeutic approach, the drug elicits a T cell response and also activates the innate immunity to kill tumor cells, and that is a very important distinction between this and other treatments.”