SYRUS Study Explores AZD0486 Safety, Dosing in Relapsed/Refractory B-Cell ALL: Ibrahim Aldoss, MD

Following the European Hematology Association (EHA) 2025 Congress in Milan, The American Journal of Managed Care^® spoke with Ibrahim Aldoss, MD, associate professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation at City of Hope, about early results from the phase 1/2 SYRUS study (NCT06137118) he presented at the meeting. The study evaluated the safety and efficacy of AZD0486 in adolescent and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).

In this clip, Aldoss provides background on the treatment and outlines the objectives of the SYRUS study.

This transcript was lightly edited; captions were auto-generated.

Transcript

For context, can you describe what AZD0486 is and what was known about its activity before the SYRUS study?

AZD0486 is a novel IgG [immunoglobin G] fully human CD3/CD19 bispecific T- cell engager. It's uniquely designed, with a low-affinity CD3 binding site to reduce cytokine release and CRS [cytokine release syndrome], but [it] also has a silent IgG4 Fc tail, which leads to a kind of long half-life, in the range of 12 to 15 days.

AZD0486, was evaluated and tested in [the] first-in-human study in patients with relapsed/refractory B-cell non-Hodgkin lymphoma, and it demonstrated activity and tolerability in both relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. [During] the last EHA [Congress], we presented the preliminary results from the dose escalation study of the SYRUS study, where we evaluated AZD0486 in patients with relapsed/refractory B-cell ALL.

What were the primary objectives of the phase 1/2 SYRUS study? What methods did you use to investigate these?

The primary objective for the dose escalation [study] was [the] safety and tolerability of AZD0486. The secondary [objectives were] efficacy, PK [pharmacokinetics], and immunogenicity.

The SYRUS study, it has 3 parts. Part A is the dose escalation [study], where we evaluated the increase [in] the target dose of AZD0486. There [is] part B, which [is] the dose optimization [study], where we select 2 dose levels that we evaluate and compare for efficacy and toxicity. Part C [is] a dose expansion [study] where we evaluated the recommended phase 2 dosing for efficacy.

[During] EHA, we only presented the first 3 dose levels from part A of the study. AZD0486 in the SYRUS study was implemented with triple-step-up dosing, or the dose was increased from day 1, then day 4, then day 8, and the target dose was given on day 15. After that, it's given as an IV [intravenous infusion] every 2 weeks.

We evaluated AZD0486 in 3 dose levels, where we evaluated 2 step-up dosing, the low step-up dosing in dose level 1, and the higher step-up dosing in levels 2 and 3. The target dose for dose level 1 was 2.4 mg. For dose level 2, [it] was 7.2 mg. For dose level 3, [it] was 15 mg.

The key eligibility criteria [are] patients aged 16 and above with relapsed/refractory B-cell ALL expressing CD19, with any level of [CD19] expression, [and] they have to fail at least 2 prior lines of therapy. The prior exposure to CD19-targeted therapies were allowed [in] the study.