Overview
This is a Phase 1/2, global multicentre, open-label, single-arm, dose escalation and dose optimisation study of AZD0486 to evaluate the safety, tolerability, and efficacy of AZD0486 monotherapy in participants with R/R B ALL who have received ≥ 2 prior lines of therapies. The study will consist of 3 parts. Part A monotherapy dose escalation. Part B dose optimisation. Part C Dose expansion at the recommended phase 2 dose (RP2D)
Eligibility
Inclusion Criteria:
- Age: 16 years and older (Part A), 12 years and older (Parts B and C).
- Participants with CD19+ B-cell Acute Lymphoblastic Leukemia by local lab with:
- Bone marrow infiltration with >/= 5% blasts
- Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.
- Philadelphia positive participants are allowed in Part A if intolerant or refractory to TKIs.
- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2
OR Lansky score more or equal to 50%.
The above is a summary, other inclusion criteria details may apply.
Exclusion Criteria:
- Active CNS involvement by B-ALL, defined by presence of ALL blasts in CSF (CNS2 and CNS3 criteria).
- Isolated extramedullary disease relapse.
- Testicular leukemia
- History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis; or prior Grade 4 neurotoxicity with CAR-T or TCE therapy.
- History of other malignancy (with certain exceptions).
- Unresolved AEs >/= Grade 2, from prior therapies
- Prior therapy with TCEs within 4 weeks, CAR T-cell therapy or autologous HSCT within 8 weeks or prior alloSCT within 12 weeks of start of therapy.
- GVHD requiring immunosuppressive therapy within 3 weeks prior to AZD0486 treatment.
The above is a summary, other exclusion criteria details may apply.