AZD0486 Shows Good Efficacy in Relapsed/Refractory Follicular Lymphoma

Atthe recent American Society of Hematology (ASH) annual meeting, data from a phase I trial of AZD0486 — a novel CD19xCD3 bispecific T-cell engager — showed high response rates and encouraging safety in relapsed/refractory follicular lymphoma patients, highlighting its potential role in sequencing strategies.

In this third of four exclusive episodes, MedPage Today brought together three expert leaders in the field, all from the Ohio State University Wexner Medical Center in Columbus. Moderator Kami Maddocks, MD, is joined by Yazeed Sawalha, MD, and David Bond, MD, for a discussion on the promising early results of AZD0486 and its evolving role in follicular lymphoma treatment.

Following is a transcript of their remarks:

Maddocks: Welcome back to this ASH 2024 Roundtable, where I’m speaking with Dr. Bond and Dr. Sawalha about new data out of ASH in follicular lymphoma. Next, I’d like to discuss the abstract [about] escalating doses of AZD0486, a novel CD19xCD3 T-cell engager. Dr. Sawalha, would you like to provide us with some thoughts on this abstract and summarize?

Sawalha: Yeah, so I thought that was very exciting data. So, this is a CD19 T-cell engager designed to bind with low affinity to CD3 T cells to potentially lower the risk of CRS [cytokine release syndrome], and then it targets CD19 on B cells similar to the other CD19-directed therapies. It was given IV [intravenously] with two step-up dosing schema to reduce the risk of CRS and ICANS [immune effector cell-associated neurotoxicity syndrome] and then it’s given every 2 weeks after for a total duration of 2 years.

This included a heavily pretreated patient population with high-risk disease. Few patients had prior CD19 CAR T cells and a very small number of patients with prior CD 20 T-cell engagers. But overall high-risk disease and a heavily pretreated patient population.

The drug is active. It showed very high response rate and the CR [complete response] rate of 85%, including in subsets with high-risk disease including POD24 [disease progression within 24 months of frontline chemoimmunotherapy]. And then also seemed very active in the very small number of patients with prior treatment with CAR T cells and T-cell engagers.

The side effects are as expected, so CRS was one of the most common ones, but most of it was grade 1 with very few cases of grade 2. ICANS in follicular lymphoma, the risk of that was very low in the double step-up dosing cohort. So, seemed like a very active drug, a very promising result, initial results, and expected safety profile for this class of drug.

Maddocks: Dr. Bond. Any additional thoughts?

Bond: Yeah, I think we’ll look forward to more follow-up as the patients continue on treatment, but so far it was very encouraging with the patients with a complete response, only two of 41 patients had relapsed, so far at least, the complete responses appear to be sustained.

I think like Dr. Sawalha highlighted, the numbers were small, but there were responses with patients that had prior T-cell engagers, so 75% of those patients responded. So also encouraging if as we look to use the T-cell engagers more as a class, that we have at least a therapy with a different target, potentially another option for patients.

Maddocks: So, I think that’s a great point. We think a lot about we are seeing more and more data about efficacy of agents in follicular lymphoma and it’s probably becoming a lot about sequencing. Any — I guess kind of a two-part question — are there any plans to further develop this and where do you see it fitting in the treatment landscape or potentially fitting into treatment landscape? Obviously, there’s probably different situations.

Sawalha: Yeah, so there’s a planned phase II trial of this drug in follicular lymphoma. So, hopefully that will confirm the high CR rates and hopefully also the durability of responses. And there are also potentially plans to bring the drug to frontline treatment of follicular lymphoma.

So, in terms of sequencing, I think we’ll have to see what’s going to happen with the CD20 T-cell engagers. They kind of have a step ahead, so maybe they’ll move to frontline maybe earlier, and then this could potentially be an option in the relapse disease. Or with time, we can maybe see this CD19 T-cell engager in the frontline as well. I think what’s important is we’re seeing these very active drugs hopefully or potentially replacing chemotherapy.

Maddocks: Yeah, that’s great. Any final thoughts? Dr. Bond?

Bond: I think it’s good to see drugs with different targets. I think we do see that now CD20 loss is one of the mechanisms of resistance with the approved bispecific antibodies. So I think having drugs that have a different target on the cell surface is attractive and overall very encouraging data. So hope to see that for patients that maintained in the phase II study.

Maddocks: Great. Yeah, it’s really great to see all these, as you mentioned, non-chemotherapy options that we’re seeing in follicular lymphoma, and hopefully we can, as you mentioned, continue to sequence these different therapies and really minimize our use of chemotherapy in this patient population. Well, great. Thank you so much for joining me today to discuss this abstract.

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