Study of AZD9829 in CD123+ Hematological Malignancies

Study Overview
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Brief Summary
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This is a modular, multicentre, open-label, Phase I/II, dose-setting study. AZD9829 will be administered intravenously as monotherapy or in combination in participants with CD123 positive hematological malignancies.

Official Title
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A Modular Phase I/II, Open-label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Antitumor Activity of AZD9829 as Monotherapy or in Combination in Patients With CD123-Positive Hematological Malignancies

Conditions
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Hematological Malignancies

Intervention / Treatment
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* Drug: AZD9829


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥18 years of age; CD123+ hematologic malignancy based on flow cytometry or immunohistochemistry by local laboratory; R/R AML; R/R HR-MDS with ≥5% bone marrow blast at time of inclusion; Had at least 1 prior line of therapy at currents histology, and have no available treatment options; ECOG performance status of ≤ 2. The above is a summary, other inclusion criteria details may apply. Exclusion Criteria: Active CNS leukemia; Previous treatment with any CD123 targeting therapy; Prior allogeneic HSCT, within 90 or cell therapy within 60 of start of therapy; Active GVHD that requires immunosuppressive treatment within 4 weeks prior to start of AZD9829; History of other malignancy(with certain exceptions); Active and uncontrolled infections; Unresolved AEs ≥2 Grade, from prior therapies. The above is a summary, other exclusion criteria details may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Module 1: Dose Escalation<br>Ascending dose level cohorts of AZD9829 in AML and MDS participants. | Drug: AZD9829<br>* AZD9829 will be administered by IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of dose limiting toxicities (DLTs). | DLTs are dose-limiting toxicities as defined in the study protocol. | Module 1 - 28 days. | 
| Safety evaluation of AZD9829: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Frequency, severity and relationship to study drug of AEs and SAEs | Module 1 - From informed consent until 30 days after last dose of AZD9829. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of AZD9829: Plasma Concentration of total antibody | Measurement of plasma concentration of conjugated and unconjugated antibody | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Plasma Concentration of total unconjugated warhead | Measurement of plasma concentration of total unconjugated warhead | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Area under the concentration time curve (AUC). | Area under the plasma concentration-time curve. | Module 1 - From date of first dose of AZD9829up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Maximum plasma concentration of the study drug (Cmax). | Maximum observed plasma concentration of AZD9829. | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Time to maximum concentration (tmax) | Time to maximum observed plasma concentration of the study drug. | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Clearance | The volume of plasma from which the study drug is completely removed per unit time. | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Half-life (t 1/2) | Terminal elimination half-life. | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA) | Evaluating the number of patients who develop anti-drug antibodies (ADA) during treatment. | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| Pharmacokinetics of AZD9829: Anti-Drug Antibodies (ADA) | Evaluating the percentage of patients who develop anti-drug antibodies (ADA) during treatment. | Module 1 - From date of first dose of AZD9829 up until 30 days post last dose. | 
| To determine the immunogenicity of AZD9829. | The number of participants who develop ADA (Anti Drug Antibodies). | Module 1 - From first dose to approximately 1 year. | 
| To determine the immunogenicity of AZD9829. | The percentage of participants who develop ADA (Anti Drug Antibodies). | Module 1 - From first dose to approximately 1 year. | 
| Overall Response Rate (ORR) | Overall response rate disease assessments in accordance with ELN2022 recommendations for AML and IWG2018 for MDS. | Module 1 - From first dose of AZD9829 until disease progression or end of the study (upto approximately 1 year) | 
| Composite Complete Response Rate (CCRR) | Composite CR rate disease assessment in accordance with ELN2022 for AML and IWG2018 for MDS. | Module 1 - From first dose of AZD9829 up to approximately 1 year. | 
| Complete remission with incomplete hematologic recovery (CRi) | The endpoint of complete remission with CRi as defined by ELN2022 criteria. | Module 1 - From first dose of AZD9829 up to approximately 1 year. | 
| Complete Response (CR) | Complete response (CR) according to ELN2022 for AML and IWG2018 for MDS. | Module 1 - From first dose of AZD9829 up to approximately 1 year. | 
| Duration of Response (DoR) | Time from first documented response until the date of relapse or death. | Module 1 -Time from first documented response until disease progression or death (approximately 1 year). | 
| Time to Response (TTR) | Time from first dose to the achievement of first overall response. Disease assessments will follow ELN2022 for AML and IWG2018 for MDS. | Module 1 - From first dose of AZD9829 until complete remission, disease progression or death (approximately 1 year). | 
| Time to Next Treatment (TTNT) | The time from the start of treatment date until the date of subsequent antileukemia therapy. | Module 1 - From first dose of AZD9829 until the date of subsequent anti-leukemia-therapy or death (approximately 1 year). | 
| Progression-free Survival (PFS) | The time from the start of treatment date until the date of disease progression or death. | Module 1 - From first dose of AZD9829 until disease progression or death (approximately 1 year). | 
| Overall Survival (OS) | The time from the start of treatment date until death. | Module 1 - From first dose of AZD9829 until death (approximately 1 year). | 
| Event-free Survival (EFS) | The time from the start of treatment date to disease progression, death, or initiation of a new anti-leukemic therapy. | Module 1 - From first dose of AZD9829 until disease progression, death, or initiation of a new anti-leukemic therapy (approximately 1 year). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AZD9829, Anti-cancer agents, Dose escalation