A Phase 1/2 Study to Evaluate the Safety and Efficacy of AZD0486 in Adolescent and Adult Participants With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia

JRCT ID: jRCT2051240250

Registered date:28/01/2025

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia
• Date of first enrollment: 27/11/2024
• Target sample size: 10
• Countries of recruitment: United States of America,Japan,Canada,Japan,Australia,Japan,South Korea,Japan,Taiwan,Japan,China,Japan,United Kingdom,Japan,Spain,Japan,Italy,Japan,Germany,Japan,France,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Part A: AZD0486 Dose Escalation
Ascending dose level cohorts of AZD0486 in B-ALL participants aged 16-80 years.
Drug: AZD0486
Investigational Product administered via intravenous infusion.

- Experimental: Part B: Dose Optimization
Up to 2 cohorts will be evaluated prior declared safe-doses and schedules in order to determine the recommended phase 2 dose (RP2D). Participants, aged 12-80 years, will receive AZD0486 IV infusions and will be randomized in a 1:1 ratio.
Drug: AZD0486
Investigational Product administered via intravenous infusion.

- Experimental: Part C: Dose Expansion
Part C will consist of 1 cohort of participants aged 12-80 years, treated with the optimal dose selected in Part B and receive IV AZD0486 monotherapy.
Drug: AZD0486
Investigational Product administered via intravenous infusion.

Outcome(s)

Primary Outcome

- Part A: Frequency of DLTs
DLTs are dose-limiting toxicities as defined in the study protocol. [Time Frame: 28 days]

- Parts A & B: Safety Evaluation of AZD0486
Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes. [Time Frame: Frequency, severity, and relationship to study drug of AEs and SAEs; dose modifications; changes in laboratory evaluations; QTc, and vital signs changes.]

- Parts B & C: Overall Response Rate (ORR)
The Primary analysis for ORR be conducted in RP2D-treated participants (in Part B and C). [Time Frame: From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months]

Key inclusion & exclusion criteria

• Age minimum: >= 12age old
• Age maximum: <= 80age old
• Gender: Both

Include criteria

- Age: 16 years to 80 years (Part A), 12 Years to 80 years (Parts B and C).

- Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression by local lab with:

1. Bone marrow infiltration with or more 5% blasts

2. Either relapsed or refractory after a minimum of 2 prior therapies or after 1 prior line of therapy if no SOC available option.

3. Philadelphia positive participants are allowed in Part A if intolerant or refractory to TKIs.

- For participants older than 16 years, Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 2. For Participants 16 years or younger, Lansky score more or equal to 50%.

The above is a summary, other inclusion criteria details may apply.

Exclude 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 we
eks 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.

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT06137118