Early SYRUS Data Highlight Safety, Efficacy of AZD0486 in Relapsed/Refractory B-Cell ALL: Ibrahim Aldoss, MD

In the second and final part of an interview with Ibrahim Aldoss, MD, of City of Hope, he summarizes key findings from the phase 1/2 SYRUS trial (NCT06137118), presented at the European Hematology Association 2025 Congress, which evaluated the safety and efficacy of AZD0486 in adolescent and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Aldoss concludes by outlining future research directions.

Watch part 1 to learn more about the treatment and the trial's objectives.

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

Transcript

What were the key findings from this study? Were there any results that particularly stood out or surprised you?

We enrolled 31 patients on the first 3 dose levels. These patients were heavily pretreated. [The] median prior lines of therapy [were] 3 prior lines of therapy. Frequently, [they] had prior blinatumomab; 52% had prior blinatumomab. [A] third of them had prior CAR [chimeric antigen receptor] T-cell therapy, and [another] third of them had prior allogeneic stem cell transplant. Frequently, they had a high disease burden before treatment.

From a safety standpoint, the treatment was well tolerated. Grade 3 and higher adverse events were in line with what we see in studies [where] we evaluated new drugs for relapsed/refractory ALL, the most common being febrile neutropenia reported in 19% of patients. [We also observed] some cytopenia and a few cases of elevation in ALT [alanine aminotransferase] and AST [aspartate aminotransferase].

We only encountered 2 dose-limiting toxicities [DLTs]. Both of them [were] prolonged cytopenia. We were able to actually continue treatments and the cancer recovery without recurrence. One of those [patients with a] DLT also developed transient grade 3 transaminitis that resolved, and [we] were able to escalate the dose and continue treatment without recurrence. We have seen low incidence of grade 2 and higher CRS [cytokine release syndrome] and ICANS [immune effector cell-associated neurotoxicity syndrome], mainly during the step-up dosing.

From the efficacy standpoint, the response was very encouraging. We have seen dose-dependent enhanced efficacy. We have seen that the CR [complete response]/CRi [complete remission with incomplete blood count recovery] rate at dose level 1 was 46%, and the majority were MRD [minimal residual disease]-negative. For dose level 2, it was 58%, and all of them were MRD-negative. [For] dose level 3, it was 83%, and all responders achieved MRD negativity.

We have seen encouraging responses in patients, even [those who were] exposed to prior CAR T-cell therapy, blinatumomab, both prior CAR [T-cell therapy] and blinatumomab.

We have seen encouraging responses in patients with extramedullary disease, something differentiated from other bispecific antibodies currently approved [for] relapsed/refractory ALL. We have seen 4 out of 5 patients with documented extramedullary disease before treatment, and they achieved remission. Only 2 patients relapsed, and both of them were treated on dose level 1, and most of the responses happened early and after the first cycle.

What are the next steps for building on these findings?

With encouraging results from the phase 1a arm of the study, now the plan is to move to the optimization phase and, eventually, to the phase 2 part of the study. Hopefully, this will lead to drug approval.

Now, there is a lot of interest, actually, [in] how we can bring this drug early in the treatment paradigm of ALL since it is a convenient drug given every other week rather than continuous infusion.