Bispecific Antibody, AZD0486 Attacks a New Target in DLBCL | Sameh Gaballa, MD | #ASH24

Hello, my name is Samah Kaballah. I'm an associate member at Moffitt Cancer Center. I'm one of the lymphoma faculty. And today at the American Society of Hematology 2024, I presented an oral abstract about AZD 0486 in patients with relapsed refractory diffused large B-cell lymphoma. So what that means is, so AZD 0486 is what we call a bispecific antibody. It's not chemotherapy and it's an advanced immunotherapy. And basically what it is, is it's an antibody that has two ends. One end attaches to T-cells inside the patient's body. So they get the medication through the intravenously through the vein. And basically the antibody, one end of it catches the T-cells inside the body and the other end attaches to the cancer cell. So it's basically hand holding the patient's own T-cells to go and kill the cancer cells. The things that are unique about this particular antibody is it targets a different target on the cancer cells other than what is currently approved. So at this time we have some antibodies that are approved, Lophidumab and Epcridumab. They're both bispecific antibodies, but they target what we call CD20. This particular bispecific antibody that I presented targets a different antigen called CD19. So it's just a different, it's attacking the cancer cells from a different angle. This is again a first in human, a phase one study. So it's relatively early data that we're presenting and it's mainly focusing on safety and also looking at the effectiveness, but it's mostly focused on effectiveness. All bispecific antibodies, they have what we call CRS, Cytocholine Release Syndrome or ICANNs, which is neurotoxicity. And these are side effects that are common to immunotherapies like other CAR T-cell therapies or other bispecific antibodies. And there are side effects that have to do with activating the immune cells. When the immune cells, when the immune system is activated because the T-cells are basically going in and trying to fight the cancer cells and kill them, they produce inflammation in the body. And this inflammation could be, you know, the patient is basically going to feel as if they're sick, like, you know, they might feel as if they have a flu. So fever, body aches, fatigue, not because they have an actual infection, but it's because their own immune system is actually fighting the cancer cells. So these, you know, the Cytocholine Release Syndrome can be mild, meaning, you know, fatigue or fevers or, you know, if it gets severe, then no, the blood pressure could drop or the oxygen levels would drop. And what we showed with the trial was with our, you know, gradual dosing schema, all patients basically had what we call low-grade CRS. So it was mostly fevers and there was no severe Cytocholine Release Syndrome that have to do with organ toxicity or dropping the blood pressure, for example. So that was one. The other toxicity that we can sometimes see with all of these immune therapies is what we call ICANs or neurotoxicity. And what that means is neurological toxicity. So patients could have, you know, some confusion or tremors or, you know, they're unable to articulate things. And the neurotoxicity seen on the trial was, again, mostly low-grade. It happened typically for about a day. Some patients had it for up to four days, but it was reversible in all patients and it was low-grade. In terms of the effectiveness of the treatment, so we did see that we had responses in a lot of patients, including patients who had failed CAR T-cell therapy, which is, you know, our most potent treatment for Diffusal Arbicillin FOMA. And also patients on this study responded, even though they had failed other bispecific antibodies that were targeting a different antigen. So this is a treatment that can potentially offer treatment options for patients who have failed other therapies, including chemotherapy, immunotherapy, CAR T-cell therapy, or bispecific antibodies. And we're very excited about it. Again, this is a first in human, a phase one study, and we're still in the process of developing this agent and looking at higher doses, trying to achieve higher effectiveness in this very difficult to treat patient population.