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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
AZD2962 will be administered orally once daily.
Research Site
Miami, Florida, United States
NOT_YET_RECRUITINGResearch Site
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Cycle 1 Day 1 up to safety follow-up (30 days after last dose) (Approximately 3 years)
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.
Time frame: 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.
AstraZeneca Clinical Study Information Center
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Tampa, Florida, United States
Research Site
Houston, Texas, United States
NOT_YET_RECRUITINGResearch Site
Heidelberg, Australia
NOT_YET_RECRUITINGResearch Site
Melbourne, Australia
RECRUITINGResearch Site
Shinagawa-ku, Japan
RECRUITINGResearch Site
Yoshida-gun, Japan
RECRUITINGResearch Site
Seoul, South Korea
WITHDRAWNResearch Site
Seoul, South Korea
WITHDRAWNResearch Site
Barcelona, Spain
RECRUITING...and 11 more locations
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: First dose up to first diagnosis of AML (Approximately 3 Years)
Plasma concentration of AZD2962
To characterise the plasma concentration of AZD2962 as monotherapy.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Cycle 1 Day 1 (each cycle is 28 days) up to EoT (Approximately 3 Years)