A Study of AZD2962, an IRAK4 Inhibitor (IRAK4 [a Body Protein] Blocker), in Participants With Haematologic Neoplasms (Blood Cancers)
PHASE1RECRUITING
The purpose of the study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD2962, an Interleukin-1 Receptor-Associated Kinase 4 (IRAK4) inhibitor, as monotherapy and in combination with other agents in participants with haematologic neoplasms.
Study details:
This is a modular study. In Module 1, the study will begin with a dose escalation of AZD2962 monotherapy in participants with myelodysplastic syndromes (MDS) and dysplastic chronic myelomonocytic leukemia (CMML). Module 1 of the study will comprise of:.
1. A Screening Period of maximum 21 days. 2.
Treatment period with 28-day cycles where each patient will receive an oral dose of AZD2962 once daily, starting on Day 1, and will continue treatment until disease progression, unacceptable toxicity, or withdrawal. 3. Safety Follow-up period after 30 days after last dose.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Participants with relapsed/refractory MDS or participants with relapsed/refractory dysplastic CMML, with peripheral blasts or bone marrow blasts < 20%, and who received one or more prior lines of therapy as per standard of care (or who exhausted locally available treatments including treatments for actionable mutations). Diagnosis must be histologically confirmed as per the WHO 2016 classification of myeloid neoplasms.
- Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
- Participants must have symptomatic disease that requires therapy and allows for objective efficacy assessments.
- Willing to provide baseline bone marrow aspirate (or biopsy if dry-tap).
- Contraceptive use by participants or participant partners should be consistent with local regulations and also comply with Clinical Study Protocol requirements.
- All women of childbearing potential must have a negative serum pregnancy test result at Screening.
Exclusion criteria
- Prior treatment with IRAK inhibitors or inhibitors of the inflammasome pathway.
- Received any antineoplastic therapy (except hydroxyurea) within 15 days prior to first dose.
- Received any strong or moderate Cytochrome P450 3A (CYP3A) inhibitors within 15 days prior to first dose.
- Received major surgery within 28 days prior to first dose, or still recovering from surgery.
- Received drugs that are known to prolong corrected QT interval (QTc) and with known risk of Torsades de Pointes, within 15 days prior to first dose.
- Received immunosuppressive medications (including Graft-Versus-Host Disease prophylaxis) within 28 days prior to first dose, or within 15 days in the case of systemic steroids (doses exceeding 10 mg/day of prednisone or equivalent).
- Received live attenuated vaccines within 28 days prior to first dose.
- Active major bleeding event.
- Any evidence of systemic disease, significant clinical disorder, or laboratory finding that make undesirable the participation in the study.
- Mean resting corrected QT interval using Fridericia's formula (QTcF) > 450 ms obtained from triplicate Electrocardiograms (ECGs) and averaged, recorded within 5 minutes. In the presence of bundle branch block, QTcF > 470 ms is applicable.
- History of intracranial bleeding within 6 months prior to first dose.
- Active gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism or excretion of oral therapy.
- History of a prior non-haematologic neoplasm (with some exceptions).
- Unresolved Grade > 2 toxicities from prior anticancer therapies (with some exceptions).
- Concurrent enrolment in another clinical study (with some exceptions).
- Known hypersensitivity to study intervention or its excipients.
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE1
Study ID
NCT07064122
Intervention or treatment
DRUG: AZD2962
Conditions
- Haematologic Neoplasms
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Research sites nearby
Closest Location:
Research Site
Select from list below to view details:
Research Site
Heidelberg, Australia
Research Site
Melbourne, Australia
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Who is running the clinical trial?
A
AstraZeneca
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
EXPERIMENTAL: Module 1- AZD2962 (Monotherapy)
| Drug: AZD2962 |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with dose limiting toxicity (DLT) | A DLT is defined as an adverse event or abnormal laboratory value occurring during the DLT-evaluation period (first 28 days of treatment). This will be evaluated to assess the safety and tolerability and also to identify optimal biological dose (OBD) of AZD2962. | From Cycle 1 Day 1 up to end of Cycle 1 (28 Days) |
| Number of participants with Adverse events (AEs) and serious AEs | To assess the safety and tolerability of AZD2962 and also to identify OBD of AZD2962. | Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years) |
| Duration of exposure | To assess the safety and tolerability of AZD2962, and also to identify OBD of AZD2962. | Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years) |
| Relative dose intensity | To assess the safety and tolerability of AZD2962, and also to identify OBD of AZD2962. | Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years) |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of participants with Objective response (OR) | For participants with MDS or CMML, OR is defined as the achievement of Best Overall Response (BOR) assessed by relevant criteria for the selected haematologic neoplasm. The OR will be assessed to estimate the efficacy of AZD2962. | First dose up to progression of disease (PD) or last evaluable assessment in the absence of progression, whichever comes first (Approximately 3 Years) |
| Duration of response (DoR) | The DoR is defined as the time from the date of first documented OR until date of first documented PD or death (by any cause in the absence of PD), regardless of discontinuation of study interventions or receiving another anticancer therapy. The DoR will be assessed to estimate the efficacy of AZD2962. | First documented response, up to the date of the first documented PD or study end, which ever comes first (Approximately 3 Years) |
| Time to Response (TTR) | The TTR is defined as the time between start of treatment and the date of documented confirmed objective response for the selected haematologic neoplasm. The TTR will be assessed to estimate the efficacy of AZD2962. | First dose up to PD or last evaluable assessment, whichever comes first (Approximately 3 Years) |
| Overall Survival (OS) | The OS is defined as the time from the date of first dose until death due to any cause regardless of whether the participant withdraws from study therapy or receives another anti-cancer therapy. The OS will be assessed to estimate the efficacy of AZD2962. | First dose up to death due to any cause (Approximately 3 Years) |
| Time to Progression to Acute myeloid leukaemia (AML) | Time to progression to AML as per World Health Organization (WHO) 2016 is defined from the time of first dose until first diagnosis of AML, regardless of discontinuation of treatment or receiving another anti-cancer therapy. This will be assessed to estimate the efficacy of AZD2962. | First dose up to first diagnosis of AML (Approximately 3 Years) |
| Plasma concentration of AZD2962 | To characterise the plasma concentration of AZD2962 as monotherapy. | Cycle 1 Day 1 (each cycle is 28 days) up to end of the treatment (EoT) (Approximately 3 Years) |
| Area under the concentration time curve (AUC). | To characterise the pharmacokinetics (PK) AUC of AZD2962 as monotherapy. | Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years) |
| Maximum plasma drug concentration (Cmax) | To characterise the PK (Cmax) of AZD2962 as monotherapy. | Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years) |
| Time to reach maximum concentration (tmax) | To characterise the PK (tmax) of AZD2962 as monotherapy. | Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years) |
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References
Clinical Trials Gov: A Study of AZD2962, an IRAK4 Inhibitor (IRAK4 [a Body Protein] Blocker), in Participants With Haematologic Neoplasms (Blood Cancers)Other trials to consider
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