C047 | SAFETY AND EFFICACY OF AZD0486 IN ADOLESCENT AND ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA: EARLY RESULTS FROM THE PHASE 1/2 SYRUS STUDY

AZD0486 is a novel IgG4 fully human CD19xCD3 bispecific T-cell with low-affinity CD3 binding reducing cytokine release from T-cell activation while preserving T-cell cytotoxicity against malignant B cells. Its activity and tolerability in R/R follicular lymphoma and diffuse large B-cell lymphoma has been demonstrated in NCT04594642. Preliminary results of a dose-escalation study of intravenous AZD0486 in R/R B-cell acute lymphoblastic leukemia (B-ALL) (SYRUS; NCT06137118). SYRUS consists of sequential dose escalation (part A), dose optimization (part B), and efficacy expansion (part C) parts. Eligible pts for part A are aged 16–80 y pts with R/R Philadelphia chromosome-positive (Ph+) or Ph-negative CD19+ B-ALL and either ≥2 prior lines of therapy (LOT) or ≥1 prior LOT and not eligible for standard of care. Part A consists of includes 3–5 dose level (DL) cohorts assessing ascending target doses (TDs) of AZD0486. AZD0486 was administered using step-up doses (SUD) based on NCT04594642. The TD was given on cycle (C) 1 day (D) 15 and every 2 wks. On January 31, 2025, TDs of 2.4 and 7.2 mg were evaluated. Investigators perform disease assessment at end of each cycle following ELN 2022/NCCN criteria using multiparametric flow cytometry (MPF; local lab) and central next-generation sequencing (NGS) for minimal residual disease (MRD) assessment. During part A, the primary study objective is the safety and tolerability of AZD0486. As of January 31, 2025, 24 pts were enrolled in part A (Ph+: n=2) (Table). In DL1, 4 of 13 (31%) pts developed CRS during SUD (2 G2) and 4 developed CRS at TD (1 G2); tocilizumab was used in 4 pts. No ICANS occurred and dose-limiting toxicity (DLT) occurred in 1 pt (G3 AST elevation on D10 and prolonged G4 cytopenia in absence of disease by D44). Rate of complete remission (CR) or CR with incomplete recovery (CRi) was 46% (6/13); 83% (5/6) were MRD negative (MRDneg) including 1 of 4 pts double-exposed to blinatumomab and CAR-T. In DL2, 8/11 (73%) pts had ≥1 CRS event during SUD (2 G2) and 2 pts had CRS (1 G2) at TD; tocilizumab was used in 4 pts. ICANS was reported in 1 pt (G2); no DLTs occurred. CR/CRi was reported in 6/9 pts (67%; all MRDneg); 2 pts in C1 are pending evaluation. In DL1/DL2, no treatment discontinuations due to AZD0486-related AEs occurred. Preliminary results from SYRUS suggest AZD0486 is active and well tolerated in pts with R/R B-ALL.