AZD0486 as Monotherapy in B-cell Acute Lymphoblastic Leukaemia (SYRUS)

AstraZeneca

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: B-cell Acute Lymphoblastic Leukemia (B-ALL)

Treatments: Drug: AZD0486

Study type: Interventional

Funder types: Industry

Identifiers

NCT06137118

D7405C00001

Details and patient eligibility

About

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)

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 12 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 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:

  1. Bone marrow infiltration with >/= 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.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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120 participants in 3 patient groups

Part A: AZD0486 Dose Escalation

Experimental group

Description:

Ascending dose level cohorts of AZD0486 in B-ALL participants aged 16-80 years.

Treatment:

Drug: AZD0486

Part B: Dose Optimization

Experimental group

Description:

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.

Treatment:

Drug: AZD0486

Part C: Dose Expansion

Experimental group

Description:

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.

Treatment:

Drug: AZD0486