Haematological Malignancies
Conditions
Keywords
Pharmacokinetics, AZD0466, Voriconazole, Drug-drug interaction
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.
Interventions
DRUGAZD0466
AZD0466 powder for concentrate for solution for infusion will be administered by IV infusion.
DRUGVoriconazole
Voriconazole film-coated tablet will be administered orally.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | From screening (Day -28 to Day 1) up to 28 days after last dose (Approximately 2.1 years) | The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed. |
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | From screening (Day -28 to Day 1) up to 28 days after last dose (Approximately 2.1 years) | The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed. |
| Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | upto 35 days | The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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) | Overall survival (OS) is defined as time from date of first dose until the date of death due to any cause. |
| 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) | Assessment of AUC to evaluate the drug-drug interaction potential between AZD0466 and the azole antifungal voriconazole. For this outcome measure, pharmacokinetics (PK) analysis set was included which consisted of all dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may affect PK. |
| Module 1: Complete Response Rate | Day 1 until post treatment follow-up (28 days after last dose) (approximately 2.1 years) | Complete response rate (CR+CRi) is defined as the percentage of participants who have a complete remission (CR) or incomplete haematological response (CRi). |
| Module 1 and Module 2: Plasma Concentration of AZD4320 | Module 1: Cycle 1 Days 1-30 (Cycle length 21 days) to Cycle 3 Days 1-28, & beyond (Cycle length 28 days); Module 2: Cycle 1 Days 1-8, Days 15-19 (Cycle length 21 days), Cycle 2 Day 1, Cycle 3 Day 1 & beyond (Cycle length 28-days) (approximately 2.1 Years) | Assessment of AZD4320 to characterise the PK profile of AZD0466 following intravenous administration (via PK profiles of the active moiety AZD4320 in plasma). |
| Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) 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) | Assessment of Cmax to evaluate the drug-drug interaction potential between AZD0466 and the azole antifungal voriconazole. For this outcome measure, PK analysis set was included which consisted of all dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may affect PK. |
| Module 1: Time to Response (TTR) | Day 1 until post treatment follow-up (28 days after last dose) (Approximately 2.1 years) | Time to response is defined as the time from date of first dose until the date of first documented CR or CRi. |
| Module 1: Duration of Response | Day 1 until post treatment follow-up (28 days after last dose) (approximately 2.1 years) | Duration of Response (DoR) will be defined as the time from the date of first documented response (CR+CRi) until date of documented progression, relapse or failure or death due to any cause. |
Countries
Australia, France, Germany, Italy, South Korea, United States
Participant flow
Recruitment details
The study was conducted in 2 modules. Module 1 of the study was conducted at 14 sites in 6 countries (Australia, France, Germany, Italy, South Korea, and United States of America \[USA\]). Module 2 of the study was conducted at 6 sites in 2 countries (Australia and USA).
Pre-assignment details
Participants who met all the inclusion and none of the exclusion criteria were enrolled in this study. All study assessments were performed as per the schedule of assessment.
Participants by arm
| Arm | Count |
|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg Participants received IV 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. | 4 |
| Module 1: AZD0466 Monotherapy- 600 mg Participants received IV 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. | 4 |
| Module 1: AZD0466 Monotherapy- 1200 mg Participants received IV 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. | 7 |
| Module 1: AZD0466 Monotherapy- 2400 mg Participants received IV 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. | 5 |
| Module 1: AZD0466 Monotherapy- 3600 mg Participants received IV 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. | 10 |
| Module 1: AZD0466 Monotherapy- 5400 mg Participants received IV 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. | 2 |
| Module 2: AZD0466 300 mg+ Voriconazole Participants received IV infusion of AZD0466 both with and without voriconazole in Cycle 1. Participants received AZD0466 alone from Cycle 2 (28 days) onwards and beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent. | 1 |
| Module 2: AZD0466 600 mg+ Voriconazole Participants received IV infusion of AZD0466 both with and without voriconazole in Cycle 1. Participants received AZD0466 alone from Cycle 2 (28 days) onwards and beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent. | 3 |
| Module 2: AZD0466 1200 mg+ Voriconazole Participants received IV infusion of AZD0466 both with and without voriconazole in Cycle 1. Participants received AZD0466 alone from Cycle 2 (28 days) onwards and beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent. | 4 |
| Module 2: AZD0466 2400 mg+ Voriconazole Participants received IV infusion of AZD0466 both with and without voriconazole in Cycle 1. Participants received AZD0466 alone from Cycle 2 (28 days) onwards and beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent. | 4 |
| Module 2: AZD0466 3600 mg+ Voriconazole Participants received IV infusion of AZD0466 both with and without voriconazole in Cycle 1. Participants received AZD0466 alone from Cycle 2 (28 days) onwards and beyond Cycle 3 until progressive disease, unacceptable toxicity, or withdrawal of consent. | 2 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 3 | 1 | 4 | 2 | 5 | 2 | 1 | 1 | 2 | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Other | 1 | 2 | 2 | 1 | 3 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Study terminated by Sponsor | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 1 | 2 | 1 | 0 |
Baseline characteristics
| Characteristic | Module 1: AZD0466 Monotherapy- 300 mg | Module 1: AZD0466 Monotherapy- 600 mg | Module 1: AZD0466 Monotherapy- 1200 mg | Module 1: AZD0466 Monotherapy- 2400 mg | Module 1: AZD0466 Monotherapy- 3600 mg | Module 1: AZD0466 Monotherapy- 5400 mg | Total | Module 2: AZD0466 300 mg+ Voriconazole | Module 2: AZD0466 600 mg+ Voriconazole | Module 2: AZD0466 1200 mg+ Voriconazole | Module 2: AZD0466 2400 mg+ Voriconazole | Module 2: AZD0466 3600 mg+ Voriconazole |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous Module 1 | 61.3 Years STANDARD_DEVIATION 20.07 | 72.3 Years STANDARD_DEVIATION 4.03 | 64.6 Years STANDARD_DEVIATION 14.98 | 63.4 Years STANDARD_DEVIATION 16.91 | 62.8 Years STANDARD_DEVIATION 10.77 | 61.5 Years STANDARD_DEVIATION 10.61 | 64.2 Years STANDARD_DEVIATION 12.99 | — | — | — | — | — |
| Age, Continuous Module 2 | — | — | — | — | — | — | 61.0 Years STANDARD_DEVIATION 19.89 | NA Years | 74.0 Years STANDARD_DEVIATION 5.2 | 40.0 Years STANDARD_DEVIATION 20.99 | 62.5 Years STANDARD_DEVIATION 17.08 | 71.0 Years STANDARD_DEVIATION 7.07 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 3 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 9 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 3 Participants | 6 Participants | 5 Participants | 9 Participants | 0 Participants | 35 Participants | 0 Participants | 3 Participants | 4 Participants | 3 Participants | 2 Participants |
| Sex/Gender, Customized Female | NA Participants | 2 Participants | 3 Participants | 3 Participants | 5 Participants | NA Participants | NA Participants | NA Participants | 0 Participants | NA Participants | NA Participants | NA Participants |
| Sex/Gender, Customized Male | NA Participants | 2 Participants | 4 Participants | 2 Participants | 5 Participants | NA Participants | NA Participants | NA Participants | 3 Participants | NA Participants | NA Participants | NA Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 1 / 4 | 4 / 7 | 2 / 5 | 5 / 10 | 2 / 2 | 1 / 1 | 1 / 3 | 2 / 4 | 2 / 4 | 1 / 2 |
| other Total, other adverse events | 4 / 4 | 4 / 4 | 6 / 7 | 5 / 5 | 9 / 10 | 2 / 2 | 1 / 1 | 3 / 3 | 3 / 4 | 4 / 4 | 2 / 2 |
| serious Total, serious adverse events | 4 / 4 | 0 / 4 | 3 / 7 | 3 / 5 | 8 / 10 | 1 / 2 | 1 / 1 | 2 / 3 | 0 / 4 | 4 / 4 | 2 / 2 |
Outcome results
Primary
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.
Time frame: From screening (Day -28 to Day 1) up to 28 days after last dose (Approximately 2.1 years)
Population: Safety analysis set consisted of all enrolled participants who received at least 1 dose of AZD0466.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE of >= CTCAE grade 3 | 4 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose interruption | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE and/or >= CTCAE grade 3 AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE of >= CTCAE grade 3 | 2 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose interruption | 1 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE and/or >= CTCAE grade 3 AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE of >= CTCAE grade 3 | 4 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE and/or >= CTCAE grade 3 AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose interruption | 2 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE | 6 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose interruption | 3 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE | 5 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related SAE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE of >= CTCAE grade 3 | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE and/or >= CTCAE grade 3 AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related AE | 8 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE with outcome death | 1 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE | 9 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE classified as a DLT | 2 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to discontinuation of AZD0466 | 3 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE | 8 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE of >= CTCAE grade 3 | 9 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE and/or >= CTCAE grade 3 AE | 9 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose interruption | 5 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related SAE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose interruption | 1 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE of >= CTCAE grade 3 | 2 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to discontinuation of AZD0466 | 1 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE and/or >= CTCAE grade 3 AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any SAE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE classified as a DLT | 1 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any AE leading to AZD0466 dose reduction | 1 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 1] | Any possibly related SAE | 1 Participants |
Primary
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.
Time frame: From screening (Day -28 to Day 1) up to 28 days after last dose (Approximately 2.1 years)
Population: Safety analysis set consisted of all enrolled participants who received at least 1 dose of AZD0466.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE and/or >= CTCAE grade 3 AE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to discontinuation of AZD0466 | 1 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE of >= CTCAE grade 3 | 1 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related AE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose interruption | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose interruption | 2 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE of >= CTCAE grade 3 | 3 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose reduction | 1 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE and/or >= CTCAE grade 3 AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related AE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related SAE | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose reduction | 1 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose interruption | 1 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE of >= CTCAE grade 3 | 3 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE and/or >= CTCAE grade 3 AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE and/or >= CTCAE grade 3 AE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE of >= CTCAE grade 3 | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE | 4 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to discontinuation of AZD0466 | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE with outcome death | 1 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related SAE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose interruption | 1 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related AE | 3 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose reduction | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to discontinuation of AZD0466 | 1 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE classified as a DLT | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE leading to AZD0466 dose interruption | 2 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE with outcome death | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE of >= CTCAE grade 3 | 2 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related deaths | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any SAE and/or >= CTCAE grade 3 AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any AE | 2 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related SAE | 1 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Module 2] | Any possibly related AE | 2 Participants |
Primary
Number of Participants With Dose-limiting Toxicity (DLT) [Module 1]
The safety and tolerability of AZD0466 in participants with advanced haematological malignancies were assessed.
Time frame: upto 35 days
Population: DLT-evaluable set consisted of participants enrolled in the dose-escalation that have received at least 3 doses of AZD0466 at the target dose level (75% of target doses from Day 8 to Day 29 in Cycle 1) and have completed the safety follow-up through the DLT evaluation period or have experienced a DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | 0 Participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | 0 Participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | 0 Participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | 0 Participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | 2 Participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Number of Participants With Dose-limiting Toxicity (DLT) [Module 1] | 1 Participants |
Secondary
Module 1 and Module 2: Plasma Concentration of AZD4320
Assessment of AZD4320 to characterise the PK profile of AZD0466 following intravenous administration (via PK profiles of the active moiety AZD4320 in plasma).
Time frame: Module 1: Cycle 1 Days 1-30 (Cycle length 21 days) to Cycle 3 Days 1-28, & beyond (Cycle length 28 days); Module 2: Cycle 1 Days 1-8, Days 15-19 (Cycle length 21 days), Cycle 2 Day 1, Cycle 3 Day 1 & beyond (Cycle length 28-days) (approximately 2.1 Years)
Population: PK set consisted of all dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may affect PK.~For PK concentration and parameter data, if there were \<3 values available at a time point or if the value was below the lower limit of quantification (BLQ), descriptive statistics were reported as 'Not calculable (NC)' or 'Not Available (NA)'.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 528.6 nanomolar (nM) | Geometric Coefficient of Variation 178.7 |
| Module 1: AZD0466 Monotherapy- 300 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 2/ Day 1 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 300 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 16220 nanomolar (nM) | Geometric Coefficient of Variation 53.05 |
| Module 1: AZD0466 Monotherapy- 300 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 2/ Day 1 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 600 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 1053 nanomolar (nM) | Geometric Coefficient of Variation 61.18 |
| Module 1: AZD0466 Monotherapy- 600 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 48910 nanomolar (nM) | Geometric Coefficient of Variation 28.88 |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 2/ Day 1 | 1371 nanomolar (nM) | Geometric Coefficient of Variation 98.4 |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 1651 nanomolar (nM) | Geometric Coefficient of Variation 179.8 |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 2/ Day 1 | 82070 nanomolar (nM) | Geometric Coefficient of Variation 17.95 |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 104700 nanomolar (nM) | Geometric Coefficient of Variation 76.62 |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 2/ Day 1 | 1872 nanomolar (nM) | Geometric Coefficient of Variation 196 |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 200400 nanomolar (nM) | Geometric Coefficient of Variation 27.12 |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 2/ Day 1 | 221400 nanomolar (nM) | Geometric Coefficient of Variation 33.8 |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 272800 nanomolar (nM) | Geometric Coefficient of Variation 22.27 |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 2/ Day 1 | 4661 nanomolar (nM) | Geometric Coefficient of Variation 83.61 |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 2/ Day 1 | 314500 nanomolar (nM) | Geometric Coefficient of Variation 25.27 |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 4117 nanomolar (nM) | Geometric Coefficient of Variation 141.6 |
| Module 1: AZD0466 Monotherapy- 5400 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 5400 mg | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 300 mg- Acute Lymphoblastic Leukaemia (ALL) | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 300 mg- Acute Lymphoblastic Leukaemia (ALL) | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 1200 mg - ALL | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 326.9 nanomolar (nM) | Geometric Coefficient of Variation 33.08 |
| Module 1: AZD0466 Monotherapy- 1200 mg - ALL | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 36150 nanomolar (nM) | Geometric Coefficient of Variation 14.97 |
| Module 1: AZD0466 Monotherapy- 1200 mg - ALL | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 2/ Day 1 | NA nanomolar (nM) | — |
| Module 1: AZD0466 Monotherapy- 3600 mg- ALL | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 84700 nanomolar (nM) | Geometric Coefficient of Variation 34.72 |
| Module 1: AZD0466 Monotherapy- 3600 mg- ALL | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 1440 nanomolar (nM) | Geometric Coefficient of Variation 11.2 |
| Module 2: AZD0466 2400 mg+ Voriconazole | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 2/ Day 1 | NA nanomolar (nM) | — |
| Module 2: AZD0466 2400 mg+ Voriconazole | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | 186100 nanomolar (nM) | Geometric Coefficient of Variation 44.69 |
| Module 2: AZD0466 2400 mg+ Voriconazole | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 2/ Day 1 | NA nanomolar (nM) | — |
| Module 2: AZD0466 2400 mg+ Voriconazole | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | 1745 nanomolar (nM) | Geometric Coefficient of Variation 62.4 |
| Module 2: AZD0466 3600 mg+ Voriconazole | Module 1 and Module 2: Plasma Concentration of AZD4320 | Released AZD4320: Cycle 1/ Day 8 | NA nanomolar (nM) | — |
| Module 2: AZD0466 3600 mg+ Voriconazole | Module 1 and Module 2: Plasma Concentration of AZD4320 | Total AZD4320: Cycle 1 /Day 8 | NA nanomolar (nM) | — |
Secondary
Module 1: Complete Response Rate
Complete response rate (CR+CRi) is defined as the percentage of participants who have a complete remission (CR) or incomplete haematological response (CRi).
Time frame: Day 1 until post treatment follow-up (28 days after last dose) (approximately 2.1 years)
Population: Intention to treat (ITT) set consisted of all enrolled participants who received at least 1 dose of AZD0466.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 600 mg | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 5400 mg | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 300 mg- Acute Lymphoblastic Leukaemia (ALL) | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 1200 mg - ALL | Module 1: Complete Response Rate | 0 Percentage of participants |
| Module 1: AZD0466 Monotherapy- 3600 mg- ALL | Module 1: Complete Response Rate | 0 Percentage of participants |
Secondary
Module 1: Duration of Response
Duration of Response (DoR) will be defined as the time from the date of first documented response (CR+CRi) until date of documented progression, relapse or failure or death due to any cause.
Time frame: Day 1 until post treatment follow-up (28 days after last dose) (approximately 2.1 years)
Population: ITT set consisted of all enrolled participants who received at least 1 dose of AZD0466.~Since none of the participants had achieved CR or CRi, DoR could not be calculated.
Secondary
Module 1: Overall Survival
Overall survival (OS) is defined as time from date of first dose until the date of death due to any cause.
Time frame: 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)
Population: ITT set consisted of all enrolled participants who received at least 1 dose of AZD0466.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Module 1: Overall Survival | 3.2 Months |
| Module 1: AZD0466 Monotherapy- 600 mg | Module 1: Overall Survival | NA Months |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 1: Overall Survival | 3.8 Months |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 1: Overall Survival | NA Months |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 1: Overall Survival | 2.4 Months |
| Module 1: AZD0466 Monotherapy- 5400 mg | Module 1: Overall Survival | 2.0 Months |
Secondary
Module 1: Time to Response (TTR)
Time to response is defined as the time from date of first dose until the date of first documented CR or CRi.
Time frame: Day 1 until post treatment follow-up (28 days after last dose) (Approximately 2.1 years)
Population: ITT set consisted of all enrolled participants who received at least 1 dose of AZD0466.~Since none of the participants had achieved CR or CRi, TTR could not be calculated.
Secondary
Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole
Assessment of AUC to evaluate the drug-drug interaction potential between AZD0466 and the azole antifungal voriconazole. For this outcome measure, pharmacokinetics (PK) analysis set was included which consisted of all dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may affect PK.
Time frame: 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)
Population: It was pre-specified by the Study Protocol to only analyze dosed participants with at least 1 reportable plasma concentration and no important AEs or protocol deviations that may impact PK for this Outcome Measure.~Due to changes in target dose levels and protocol deviations affecting derivation of PK parameters, AUC could not be statistically assessed (summary statistics or inferential statistical comparisons), as no participant met pre-specified criteria for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA hours*nanomole/liter (h*nmol/L) |
| Module 1: AZD0466 Monotherapy- 600 mg | Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA hours*nanomole/liter (h*nmol/L) |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA hours*nanomole/liter (h*nmol/L) |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA hours*nanomole/liter (h*nmol/L) |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 2: Area Under the Plasma Concentration-curve (AUC) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA hours*nanomole/liter (h*nmol/L) |
Secondary
Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole
Assessment of Cmax to evaluate the drug-drug interaction potential between AZD0466 and the azole antifungal voriconazole. For this outcome measure, PK analysis set was included which consisted of all dosed participants with reportable plasma concentrations and no important AEs or protocol deviations that may affect PK.
Time frame: 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)
Population: It was pre-specified by the Study Protocol to only analyze dosed participants with at least 1 reportable plasma concentration and no important AEs or protocol deviations that may impact PK for this Outcome Measure.~Due to changes in target dose levels and protocol deviations affecting derivation of PK parameters, Cmax could not be statistically assessed (summary statistics or inferential statistical comparisons), as no participant met pre-specified criteria for analysis.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Module 1: AZD0466 Monotherapy- 300 mg | Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA nanomole (nmol)/liter (L) |
| Module 1: AZD0466 Monotherapy- 600 mg | Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA nanomole (nmol)/liter (L) |
| Module 1: AZD0466 Monotherapy- 1200 mg | Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA nanomole (nmol)/liter (L) |
| Module 1: AZD0466 Monotherapy- 2400 mg | Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA nanomole (nmol)/liter (L) |
| Module 1: AZD0466 Monotherapy- 3600 mg | Module 2: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320 After Administration of AZD0466 Alone and in Combination With Voriconazole | NA nanomole (nmol)/liter (L) |