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

NCT04865419 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: D8241C000012020-005106-25
• Study Type: interventional
• Target: 46
• Locations: 6 countries
• Sites: 15

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.

Conditions

Haematological Malignancies

Keywords

Pharmacokinetics; AZD0466; Voriconazole; Drug-drug interaction

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1]

  The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed.

  From screening (Day -28 to Day 1) up to 28 days after last dose (Approximately 2.1 years)

• Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2]

  The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed.

  From screening (Day -28 to Day 1) up to 28 days after last dose (Approximately 2.1 years)

• Number of Participants With Dose-limiting Toxicity (DLT) [Module 1]

  The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed.

  upto 35 days

Secondary Outcomes (7)

• Module 1: Complete Response Rate

  Day 1 until post treatment follow-up (28 days after last dose) (approximately 2.1 years)

• Module 1: Time to Response (TTR)

  Day 1 until post treatment follow-up (28 days after last dose) (Approximately 2.1 years)

• Module 1: Duration of Response

  Day 1 until post treatment follow-up (28 days after last dose) (approximately 2.1 years)

• Module 1: Overall Survival

  Day 1 until post treatment follow-up (28 days after last dose) and survival follow-up (every month after last dose) (approximately 2.1 years)

• Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole

  Cycle 1 Days 1, 2, 3, 4, 8 and days 15, 16, 17, 18, 19, and Cycle 2 Day 1, Cycle 3 Day 1 and beyond (Cycle length 28-days) (approximately 2.1 years)

Study Arms (2)

Module 1: AZD0466 monotherapy

EXPERIMENTAL

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.

Drug: AZD0466

Module 2: AZD0466 + Voriconazole

EXPERIMENTAL

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.

Drug: AZD0466; Drug: Voriconazole

Interventions

AZD0466 DRUG

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

Module 1: AZD0466 monotherapy; Module 2: AZD0466 + Voriconazole

Voriconazole DRUG

Voriconazole film-coated tablet will be administered orally.

Module 2: AZD0466 + Voriconazole

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (15)

Research Site

Duarte, California, 91010, United States

Location

Research Site

Jacksonville, Florida, 32224, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Columbus, Ohio, 43210, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Melbourne, 3004, Australia

Location

Research Site

Parkville, 3050, Australia

Location

Research Site

Pessac, 33604, France

Location

Research Site

Aachen, 52074, Germany

Location

Research Site

Heidelberg, 69120, Germany

Location

Research Site

Kiel, 24105, Germany

Location

Research Site

Bologna, 40138, Italy

Location

Research Site

Meldola, 47014, Italy

Location

Research Site

Rozzano, 20089, Italy

Location

Research Site

Busan, 47392, South Korea

Location

Related Links

• Redacted CSP
• Redacted SAP
• Redacted CSR synopsis

MeSH Terms

Interventions

AZD0466; Voriconazole

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Trial terminated based on benefit-risk profile assessment. Due to early termination of the study, Module 1 Part A and Module 2 were conducted, Module 1 Part B was not started.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Nitin Jain, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2021
• First Posted: April 29, 2021
• Study Start: June 11, 2021
• Primary Completion: August 8, 2023
• Study Completion: August 8, 2023
• Last Updated: June 15, 2025
• Results First Posted: June 15, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to our disclosure commitment at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patientlevel data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com /ST/Submission/Disclosure.

Locations

AU (2); FR (1); DE (3); IT (3); US (5); KR (1)