Study of AZD0466 Monotherapy or in Combination in Patients With Advanced Haematological Malignancies

NCT ID: NCT04865419

Last Updated: 2025-06-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-06-11
• Study Completion Date: 2023-08-08

Brief Summary

The purpose of the study is to the evaluate safety, tolerability, pharmacokinetics (PK), and efficacy of AZD0466 as monotherapy in partciapants with advanced haematological malignancies and also to assess drug-drug interaction (DDI) potential between AZD0466 and the azole antifungal voriconazole.

Detailed Description

The study consists of 2 individual modules as: Module 1 (AZD0466 monotherapy), and Module 2 (DDI study of AZD0466 with voriconazole).

Eligible participants will be assigned to study treatments across Modules 1 and 2.

1. Module 1: AZD0466 monotherapy will include 2 parts- Part A dose escalation cohorts and Part B dose expansion cohorts. Initiation of Part B will depend on the evaluation of safety, tolerability, and PK in Part A.

2. Module 2: AZD0466 and voriconazole DDI study.

All participants will receive AZD0466, and administration will continue until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment.

Conditions

Haematological Malignancies

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Module 1: AZD0466 monotherapy

Participants will receive intravenous infusion of AZD0466 monotherapy once weekly during Cycle 1 (35 days), Cycle 2 (28 days) and Cycle 3 (28 days) and also beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent.

Group Type: EXPERIMENTAL

AZD0466

Intervention Type: DRUG

AZD0466 powder for concentrate for solution for infusion will be administered by IV infusion.

Module 2: AZD0466 + Voriconazole

Participants may receive IV infusion of AZD0466 in combination with or without voriconazole during Cycle 1 (21 days), and Cycle 2 (28 days) and Cycle 3 (28 days) and also beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent.

Group Type: EXPERIMENTAL

AZD0466

Intervention Type: DRUG

AZD0466 powder for concentrate for solution for infusion will be administered by IV infusion.

Voriconazole

Intervention Type: DRUG

Voriconazole film-coated tablet will be administered orally.

Interventions

AZD0466

AZD0466 powder for concentrate for solution for infusion will be administered by IV infusion.

Intervention Type: DRUG

Voriconazole

Voriconazole film-coated tablet will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Diagnosis of acute myeloid leukaemia (AML) or acute lymphoblastic leukaemia (ALL), or intermediate or higher risk myelodysplastic syndrome (MDS; Part A only), which is histologically proven based on criteria established by the World Health Organization (WHO) as documented by medical records. for which there are limited treatment options known to provide clinical benefit.
• Eastern cooperative oncology group performance status ≤2. Performance status must not have deteriorated by ≥2 levels within 2 weeks after providing informed consent.
• Predicted life expectancy ≥8 weeks.
• Adequate organ function at screening as per the protocol defined criteria.
• Adequate cardiac function as demonstrated by LVEF > 50% on screening cardiac multigated acquisition, magnetic resonance image or echocardiogram.
• Willing and able to participate in all required study evaluations and procedures including receiving IV administration of study treatment and admission to the hospital, when required, for administration of study treatment and monitoring.
• For inclusion in the genetic component of the study, participants must fulfil protocol defined criteria.
• White blood cell count must be <10 x 10^9/L prior to the first dose in Cycle 1, Day 1. Treatment with hydroxyurea during screening and Cycle 1 to control white blood cell count is permitted.
• Women of childbearing potential and men should use protocol defined contraceptive measures.

Exclusion Criteria

• Unresolved toxicity from prior anticancer therapy of Common Terminology Criteria for Adverse Events Grade ≥2. Participants with Grade 2 neuropathy or Grade 2 alopecia are eligible.
• Active idiopathic thrombocytopenic purpura.
• Stem cell transplant < 100 days prior to the first dose of study treatment.
• Immunosuppression for graft versus host disease (GVHD) or GVHD prophylaxis within 4 weeks prior to the first dose of study treatment.
• Active central nervous system (CNS) leukaemia/leptomeningeal disease/spinal cord compression. Participants who have a history of CNS leukaemia must be free of CNS leukaemia for >30 days prior to the first dose of study treatment, and the most recent 2 lumbar punctures must be negative for leukaemic cells, to be eligible.
• Known uncontrolled infection with cytomegalovirus (CMV) infection (positive CMV Immunoglobulin M (IgM) and/or positive polymerase chain reaction (PCR) result).
• Active infection including human immunodeficiency virus, Hepatitis B, Hepatitis C, or severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).
• As judged by the Investigator: any evidence of severe or uncontrolled systemic diseases, (eg, severe hepatic impairment, interstitial lung disease [bilateral, diffuse, parenchymal lung disease]); current unstable or uncompensated respiratory or cardiac conditions; Uncontrolled hypertension; history of, or active, bleeding diatheses (eg, haemophilia or von Willebrand disease); uncontrolled active systemic fungal, bacterial, or other infection.
• Any of the given cardiac criteria: history of myocarditis within one year of study entry, or heart failure New York Heart Association Functional Classification Class 3 or 4; mean resting corrected QT interval (QTcF) ≥470 msec obtained from 3 electrocardiogram (ECGs), in the absence of a cardiac pacemaker; abnormalities in rhythm, conduction or morphology of resting ECG; any factors that increase the risk of QTc prolongation or risk of arrhythmic events such congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age.
• History of another life-threatening malignancy ≤2 years prior to first dose of study treatment. The following are permitted: myelodysplastic syndrome or myeloproliferative neoplasm (including chronic myelomonocytic leukaemia [CMML]); malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and considered to be at low risk of recurrence by the treating physician; adequately treated lentigo malignant melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer; adequately treated carcinoma in situ without current evidence of disease.
• Any of the mentioned procedures or conditions currently or in the 6 months prior to the first dose of study treatment: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other CNS bleeding.
• Treatment with any of the mentioned therapy: radiotherapy less than 3 weeks prior to first study treatment; chemotherapy within ≤14 days or 5 half-lives prior to the first dose of study treatment. Treatment with high-dose steroids for primary malignancy control is permitted but must be discontinued at least 2 days prior to the first dose of study treatment. Treatment with hydroxyurea is permitted; immunotherapies and cellular therapies within 4 weeks prior to the first dose of study treatment; investigational drugs within ≤14 days or 5 half-lives (whichever is shorter) prior to the first dose of study treatment; major surgery (excluding placement of vascular access) ≤21 days, or minor surgical procedures ≤7 days, prior to the first dose of study treatment. No waiting is required mentioned implantable port or catheter placement; prescription or non-prescription drugs or other products known to be sensitive substrates of BCRP, OCT2, OAT3, OATP1B1, OATP1B3, CYP2B6, CYP2C8, CYP2C9 or CYP2D6, or reversible moderate or strong CYP3A inhibitors, which cannot be discontinued within 5 half-lives prior to the first dose of study treatment and withheld throughout the study until 14 days after the last dose of AZD0466; moderate or strong mechanism-based inhibitors or inducers of CYP3A4 which cannot be discontinued within 5 half-lives plus of the specific drug 12 days of the drug prior to the first dose of study treatment and withheld until 14 days after the last dose of AZD0466; concurrent anti-coagulation therapy, including aspirin and heparin, which cannot be stopped; medications with known risk of Torsades de Pointes which cannot be discontinued within 5 half-lives of the first dose of study treatment and withheld until 14 days after the last dose of AZD0466; IV anti infection treatment within 14 days before first dose of study treatment.
• History of hypersensitivity to polyethylene glycol (PEG), PEGylated products or drugs with a similar chemical structure or class to AZD0466 or other BH3 mimetic.

Module 2:

• Patients for whom treatment with voriconazole is contraindicated per the local prescribing information must not enter the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 130 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nitin Jain, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas MD Anderson Cancer Center 1515 Holcombe Boulevard, Unit 431 Houston, Texas 77030 United States of America

Locations

Research Site

Duarte, California, United States

Research Site

Jacksonville, Florida, United States

Research Site

Chicago, Illinois, United States

Research Site

Columbus, Ohio, United States

Research Site

Houston, Texas, United States

Research Site

Melbourne, , Australia

Research Site

Parkville, , Australia

Research Site

Pessac, , France

Research Site

Aachen, , Germany

Research Site

Heidelberg, , Germany

Research Site

Kiel, , Germany

Research Site

Bologna, , Italy

Research Site

Meldola, , Italy

Research Site

Rozzano, , Italy

Research Site

Busan, , South Korea

Countries

United States; Australia; France; Germany; Italy; South Korea

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Redacted CSP

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Redacted SAP

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Redacted CSR synopsis

Other Identifiers

2020-005106-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

D8241C00001

Identifier Type: -

Identifier Source: org_study_id