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ASH 2021 | Preliminary results of lemzoparlimab, an anti-CD47 antibody in R/R NHL

Current anti-CD47 antibodies such as magrolimab will have anemia as a side effect due to the blockade of CD47, utilized by older erythrocytes for elimination. Amitkumar Mehta, MD, UAB School of Medicine, Birmingham, AL, presents findings from a Phase Ib trial (NCT03934814) of lemzoparlimab, a novel anti-CD47 antibody, in patients with relapsed/refractory non-Hodgkin’s lymphoma. Patients were administered lemzoparlimab with rituximab in a 3+3 dose escalation trial, and lemzoparlimab demonstrated promising efficacy and safety across patients with diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and follicular lymphoma (FL). This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

So lemzoparlimab is an anti-CD47 antibody. If you see there are many anti-CD47 antibodies. And anti-CD47 antibody blocks the ‘don’t eat me’ signal, which is another or next-generation of checkpoint inhibitors. So when this signal is blocked, technically macrophages attack the cancer cell and kind of phagocytoze them. And the downside of prior anti-CD47, like magrolimab is that the antibody also cross-reacts with the CD47 expressed on older red blood cells...

So lemzoparlimab is an anti-CD47 antibody. If you see there are many anti-CD47 antibodies. And anti-CD47 antibody blocks the ‘don’t eat me’ signal, which is another or next-generation of checkpoint inhibitors. So when this signal is blocked, technically macrophages attack the cancer cell and kind of phagocytoze them. And the downside of prior anti-CD47, like magrolimab is that the antibody also cross-reacts with the CD47 expressed on older red blood cells. So in those patients, what happens is that older red blood cells, they also get eliminated and therefore, these patients may develop anemia. And which was also noted with prior other anti-CD47.

Lemzoparlimab is a little bit different as it does not interact with it. It attaches to a different epitope. So it does not interact with a red blood cell CD47. And therefore the anemia which is seen in initial dosage is not seen with lemzoparlimab. Now in other CD47, therefore, the other strategy of priming dosage was developed where a tiny dose, like one milligram was given to eliminate those red blood cells and then kind of assess the hemoglobin and then go on a bigger dose afterwards. Lemzoparlimab, we did not have to do that because it does not interact with the CD47 present on red blood cells. So there was no need of a priming dose in those patients.

So this was a Phase I study where we enrolled about eight or nine patients, and it was 3+3 design. Lemzoparlimab was evaluated in combination with rituximab in two different dosage, 20 milligrams per kilogram, as well as 30 milligrams per kilogram. There was one patient who had DLT and it was mainly at disease progression, but the investigator thought that this was related to lemzoparlimab, but otherwise there was no DLT noted. We could expand it to 30 milligrams per kilogram dosage, and we’re going to expand it further in a broad phase two study involving different kinds of B-cell non-Hodgkin lymphomas.

The initial activity we saw was very impressive – The disease control rate so to speak more than stable disease was 100% in patients with, follicular lymphoma, large cell lymphoma, as well as mantle cell lymphoma. Of course, the patient numbers were very small, but we got a good indication in this patient population and two of the patients who were rituximab refractory also had response. So overall we were very encouraged by the responses of lemzoparlimab in combination with rituximab in B-Cell non-Hodgkin lymphoma.

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