AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia
- Registration Number
- NCT06137118
- Lead Sponsor
- AstraZeneca
- Brief Summary
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)
- Detailed Description
This dose escalation and optimization study is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy in r/r B-ALL.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 120
-
Age: 16 years and older (Part A), 12 years and older (Parts B and C).
-
Participants with B-cell Acute Lymphoblastic Leukemia with CD19 expression 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.
-
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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part A: AZD0486 Dose Escalation AZD0486 Ascending dose level cohorts of AZD0486 in B-ALL participants aged 16-80 years. Part B: Dose Optimization AZD0486 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. Part C: Dose Expansion AZD0486 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.
- Primary Outcome Measures
Name Time Method Part A: Frequency of DLTs 28 days DLTs are dose-limiting toxicities as defined in the study protocol
Parts A & B: Safety Evaluation of AZD0486 From signing of informed consent through completion of study treatment, an average of 8 months 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) From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 24 months The Primary analysis for ORR be conducted in RP2D-treated participants (in Part B and C).
- Secondary Outcome Measures
Name Time Method Part A: Objective Response Rate (ORR) From First dose to end of treatment or data cutoff, whichever comes first, assessed up to 12 months Overall response rate (ORR) is defined as proportion of participants who achieve overall response (CR/CRi).
Parts A, B, C: Duration of response (DoR) Up to 36 months Date of first documented CR/CRi until the date of relapse or death
Parts A, B, C: CR rate at any time during the study From first dose until end of study, up to 36 months CR rate as defined as the percentage of participants achieving CR at any time by NCCN criteria
Parts A, B, C: Event-free survival (EFS) From first dose until end of study, up to 36 months Event-free survival is defined as the time from the date of the first dose until the date of a relapse after achieving a CR/ CRi, or death due to any cause.
Parts A, B, C: Overall survival (OS) From first dose until end of study, up to 36 months OS measured from first dose of study drug until death
Parts B &C: CR MRD-negative rate First dose until end of study, up to 24 months Number of patients who achieve CR MRD-negative by NGS at any time on study
Parts A, B, C: PK Characterization of AZD0486 From first dose until end of study, up to 36 months Derived PK Parameter: CL of AZD0486
Part C: Safety Evaluation of AZD0486 From signing of informed consent through completion of study treatment, an average of 8 months 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: Subsequent alloSCT From first dose until end of study, up to 24 months Number of patients who after achieve CR/CR underwent an alloSCT
Parts A, B, & C: PK characterization of AZD0486 From first dose until end of study, up to 36 months Derived PK parameter: AUC
Parts A, B & C: PK Characterization of AZD0486 From first dose until end of study, up to 36 months Derived PK parameter: Cmax
Parts A, B, C: ADA characterization of AZD0486 Consent until 36 months after first dose Summary of pre-existing and treatment-induced ADAs for AZD0486 (positive or negative, titres)
Trial Locations
- Locations (1)
Research Site
🇬🇧Surrey, United Kingdom