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ASH 2021 | Epcore CLL-1: Phase I trial of epcoritamab in r/r CLL

Arnon Kater, MD, PhD, University of Amsterdam, Amsterdam, Netherlands, discusses the Phase I trial (NCT04623541) of epcoritamab, a CD3/CD20 bispecific monoclonal antibody, in patients with relapsed/refractory chronic lymphocytic leukemia. The dose escalation stage of the study reported that doses of 24mg and 48mg were safe, with moderate toxicity. The trial is currently in the dose-expansion stage, with early signs of clinical efficacy in some patients. This interview took place at the 63rd ASH Annual Meeting and Exposition congress in Atlanta, GA.

Transcript (edited for clarity)

Until now, we discussed all different combinations on targeted therapy without chemotherapy. So you have the ingredients venetoclax, you have the ingredient BTK inhibitor, and you have the ingredient monoclonal antibodies. But we still know that we don’t cure those patients. And if you compare CLL to all the other diseases that are discussed in this ASH, it’s that we are I think very much on top of targeted therapy, but so far CLL is not that successful in engaging T-cells in therapy, which actually might be very promising...

Until now, we discussed all different combinations on targeted therapy without chemotherapy. So you have the ingredients venetoclax, you have the ingredient BTK inhibitor, and you have the ingredient monoclonal antibodies. But we still know that we don’t cure those patients. And if you compare CLL to all the other diseases that are discussed in this ASH, it’s that we are I think very much on top of targeted therapy, but so far CLL is not that successful in engaging T-cells in therapy, which actually might be very promising.

And the reason that so far, it has not been very successful is that, we and other groups have shown that there is an acquired T-cell dysfunction in this disease, which might hamper responses to T-cell directed therapies. And what we now are performing is a Phase I trial with epcoritamab. And epcoritamab is a CD3, CD20 monoclonal antibody, or bispecific antibody, that already is successfully tested in diffuse large B-cell lymphoma.

And we did a dose escalation Phase I study in CLL. Patients were very heavily treated. A median of six or more treatments, which is really a heavily treated patient group. And we started with 24 milligrams and went to up to 48 milligrams because we didn’t know what to expect either, you can say because for a lot more of circulating tumor cells, you might get actually more toxicities, CRS or, or ICANS and neurologic toxicities. And you can say that maybe because of this problem with the T-cells, you might actually have lower efficacy. Well, so far we have seen that 24 milligrams is safe, but 48 milligrams is also safe and we finish the dose escalation, and we are now in the dose expansion cohort where we also include Richter’s transformation patients. But so far, what we can say is that the toxicity was actually very moderate and quite similar to DLBCL studies.

So we did see CRS, but no grade threes. We see some patients’ neurological symptoms, but also very, very minor. And we did see first signs of activity with PRs and even one CR thus far. And it’s all very early, still. So the most important message I think of this poster is that yes, we can do it in CLL. We have probably found their correct dose and toxicities are not different than in DLBCL. And there is an early sign of clinical efficacy as well.

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