Advanced Haematological Malignancies
Conditions
Keywords
AZD4573, Anti-cancer Agents, Sequential dose-setting and expansion treatment
Brief summary
This is a modular, multicentre, open-label, non-randomised, Phase I/II, dose-setting and expansion study including an intra-participants dose ramp up. AZD4573 will be administered intravenously, in novel combinations with anti-cancer agents, to participants with relapsed/refractory (r/r) haematological malignancies.
Detailed description
In Module 1 Part A (dose-setting), this study module will enrol participants with r/r Diffuse large B-cell lymphoma (DLBCL) or r/r Marginal zone lymphoma (MZL) who have failed prior therapy(ies), are not eligible for curative treatment options, for whom there is no standard therapy available, and will initially explore once weekly administration of AZD4573 at up to three target dose levels in combination with oral acalabrutinib 100 mg twice daily. The primary objective of Part A will be to identify the maximum tolerated dose and/or Recommended Phase II dose (RP2D) for further evaluation in Part B. A 5-week DLT-assessment period will incorporate the whole of Cycle 1 in Part A, including the dose ramp up and the first 3 weeks at the target dose. In Module 1 Part B (expansion), separate expansion cohorts for participants with Germinal Centre B-cell (GCB) and non-GCB DLBCL subtypes will be opened at the RP2D. In Module 2, this study module will enroll participants with r/r Mantle Cell Lymphoma (MCL) who have failed at least one line of prior therapy, are not eligible for curative treatment options. Module 2, Part A consist of AZD4573 monotherapy (Period 1) followed by AZD4573 + acalabrutinib combination treatment (Period 2). Period 1: AZD4573 will be administered weekly (12 mg, infusion). Period 2: AZD4573 (RP2D from Module 1) will be administered (weekly) in combination with oral acalabrutinib 100 mg twice daily. Cycle 1 of each dosing period has a duration of 5 weeks; subsequent cycles have a duration of 3 weeks. The AZD4573 monotherapy (Period 1) includes an intra-patient ramp up; participants will receive AZD4573 at Cycle 1 Week 1, Cycle 1 Week 2, and Cycle 1 Week 3 in 3 dose escalation manner (6, 9 and 12 mg respectively). Part A, Period 1 of Module 2 aims to confirm the AZD4573 monotherapy RP2D in MCL participants. In Period 2, the safety and tolerability of the RP2D of AZD4573 + acalabrutinib established in Module 1 will be assessed in participants with MCL. The study design of Part B of Module 2 will be determined from the data emerging from Part A.
Interventions
DRUGAZD4573
AZD4573 will be administered as an absolute (flat) dose, 2-hour (± 15 minutes) IV infusion once weekly (as monotherapy for Module 2 only) and in combination with orally administered acalabrutinib twice daily continuously. For both Part A and Part B of this study, Cycle 1 consists of 5 weeks, with a dose ramp-up. Subsequent cycles are 21 days (3 weeks) with once weekly dosing of AZD4573 in combination with acalabrutinib twice daily continuously (in Module 1 and Module 2, period 2).
DRUGAcalabrutinib
Oral Acalabrutinib capsule will be administered twice daily continuously from Day 1 of Cycle 1 Week 1 in combination with AZD4573.
Sponsors
Parexel
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
- Core * Participant must be ≥ 18 years of age at the time of signing the informed consent. * Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Must have received at least one prior line of therapy for the treatment of current disease and a clinical study is the best option for next treatment based on prior response and/or tolerability. * Documented active disease requiring treatment that is r/r defined as: Recurrence of disease after response to at least one prior line(s) of therapy or Progressive disease after completion of or on the treatment regimen preceding entry into the study or Disease that did not achieve an objective response (overall response of CR or PR). * Adequate haematological function. * Adequate organ function at Screening. * Uric acid level \< upper limit of normal (ULN). Inclusion Criteria - Module 1 \- Participants with histologically confirmed, r/r DLBCL, or r/r MZL, for whom a clinical study is the best option for next treatment based on response and/or tolerability to prior lines of therapy. PART A • Participants with r/r DLBCL, including subtypes such as DLBCL not otherwise specified \[NOS\], high-grade B cell lymphoma \[HGBCL\], primary mediastinal large B-cell lymphoma \[PMBCL\], or large B cell lymphoma transformed from indolent B-cell lymphomas (including but not limited to Richter Syndrome, transformed Follicular Lymphoma, transformed MZL), or r/r MZL: participants with r/r MZL are eligible as well. In case fresh tumor biopsy is not available, archival tumor samples are acceptable, if done with 24 months PART B • Participants with r/r de novo r/r DLBCL only, fresh tumor biopsy, done at screening or within 60 days before planned 1st dosing, unless there was any anticancer treatment given after tumor biopsy, but prior initiated study treatment. * Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy. * Participants must have failed at least two prior therapies for the treatment of current disease. Participants shall not be eligible for curative treatment options, and have no standard therapy available (including CAR-T cell therapy). * Adequate haematologic function at screening: No growth factor support within 14 days prior to the date of the screening laboratory assessment; No transfusions within 7 days prior to the date of the screening laboratory assessment. * Optional tumour biopsy on study: Participants are also encouraged to consent to and undergo an optional tumour biopsy at disease progression to support correlative biomarker studies. * All participants must be willing and able to provide mandatory baseline bone marrow biopsy/aspirate. Inclusion Criteria - Module 2 \- Participants with histologically confirmed r/r MCL for whom a clinical study is the best option (in the opinion of the investigator) for next treatment based on response and/or tolerability to prior lines of therapy. PART A * Participants with r/r MCL: * Diagnosis must be confirmed by biopsy and be immunohistologically characterised. * Tumour tissue must also be available for sending to AstraZeneca for pathology testing. * Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy * Participants must have failed at least one prior therapy for the treatment of current disease and not be eligible for treatment with curative intent (e.g. allogenichaematopoietic cell transplantation \[HCT\]). Eligible participants include both BTKi-naïve and BTKi-exposed. * Adequate haematologic function at screening: No growth factor support within 14 days prior to the date of the screening laboratory assessment; No transfusions within 7 days prior to the date of the screening laboratory assessment. * Optional tumour biopsy on study: Participants are also encouraged to consent to and undergo an optional tumour biopsy at disease progression to support correlative biomarker studies. * All participants must be willing and able to provide mandatory baseline bone marrow biopsy/aspirate.
Exclusion criteria
- Core * Participants with non-secretory myeloma. * With the exception of alopecia, any unresolved non-haematological toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment. * Presence of, or history of, central nervous system (CNS) lymphoma, leptomeningeal disease, or spinal cord compression. * History of prior non-haematological malignancy except for the following: Malignancy treated with curative intent and with no evidence of active disease for \>1 year before Screening and felt to be at low risk for recurrence by treating physician; Adequately treated lentigo maligna melanoma without evidence of disease or adequately controlled non-melanomatous skin cancer; Adequately treated carcinoma in situ without current evidence of disease. * Any evidence of severe or uncontrolled systemic disease (eg, severe hepatic impairment, interstitial lung disease), or current unstable or uncompensated respiratory or cardiac conditions, or uncontrolled hypertension, history of, or active, bleeding diatheses or uncontrolled active systemic fungal, bacterial, viral, or other infection, or IV anti infective treatment within two weeks before first dose of study drug. * Known history of infection with human immunodeficiency virus (HIV). * Serologic status reflecting active hepatitis B or C infection. * Any of the following cardiac criteria: Resting QT interval corrected using Fridericia's formula (QTcF) ≥ 470 msec obtained from a single electrocardiogram (ECG); any clinically important abnormalities in rhythm (except for participants with a pacemaker in place), conduction or morphology of resting ECG); any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death under 40 years of age. Concomitant medications known to prolong QTc should be used with caution and cannot be used starting with the first dose of study drug and through the DLT-assessment period (Part A) or during the scheduled ECG assessments. * History of severe allergic or anaphylactic reactions to BH3 mimetics or history of hypersensitivity to active or inactive excipients of study treatment. * Documented confirmation and ongoing treatment of adrenal gland insufficiency or pancreatitis. * History, within the previous 6 months prior to first dose, of: coronary artery bypass graft; angioplasty; vascular stent; myocardial infarction; angina pectoris; congestive heart failure (New York Heart Association Class ≥ 2); ventricular arrhythmias requiring continuous therapy; atrial fibrillation, which is judged as uncontrolled by the treating physician; haemorrhagic or thrombotic stroke, including transient ischaemic attacks or any other CNS bleeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Module 1: Number of Participants With Adverse Events | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | Safety and tolerability of AZD4573 in combination with acalabrutinib was assessed. |
| Module 1: Overall Response Rate (ORR) of AZD4573 in Combination With Acalabrutinib | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | Overall response rate (ORR), defined as the proportion of participants who have a tumour response (complete response \[CR\] and partial response \[PR\]). |
| Module 2: Number of Participants With Adverse Events | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | Assessed safety and confirmed the RP2D of AZD4573 monotherapy in MCL participants and assessed the safety and tolerability of AZD4573 in combination with acalabrutinib in participants administered AZD4573 monotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Module 1: Overall Survival (OS) | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | OS, defined as the time from first dose until the date of death from any cause. |
| Module 1: Cmax of AZD4573 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax). |
| Module 1: Cmax of Acalabrutinib | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax). |
| Module 1: Cmax of ACP-5862 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax). |
| Module 1: AUClast of AZD4573 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast). |
| Module 1: AUClast of Acalabrutinib | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast). |
| Module 1: AUClast of ACP-5862 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast). |
| Module 1: AUCinf of AZD4573 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf). |
| Module 1: Complete Response (CR) Rate | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | CR is defined as no detectable evidence of tumor, according to the revised response criteria for malignant lymphoma. |
| Module 1: AUCinf of ACP-5862 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf). |
| Module 1: Tmax of AZD4573 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Time to reach peak or maximum observed concentration following drug administration (tmax). |
| Module 1: Tmax of Acalabrutinib | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Time to reach peak or maximum observed concentration following drug administration (tmax). |
| Module 1: Tmax of ACP-5862 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Time to reach peak or maximum observed concentration following drug administration (tmax). |
| Module 1: t1/2 of AZD4573 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2). |
| Module 1: t1/2 of Acalabrutinib | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2). |
| Module 1: t1/2 of ACP-5862 | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2). |
| Module 1: AUCinf of Acalabrutinib | Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1 | Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf). |
| Module 1: Duration of Response (DoR) | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | DoR, defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first. |
| Module 1: Progression Free Survival (PFS) | From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years) | PFS, defined as the time from first dose date to documented disease progression, or death from any cause, whichever occurs first |
Countries
Australia, Canada, France, Ireland, Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted from 17 February 2021 to 08 September 2023. Module 1 was conducted at 17 study centers in 10 countries. Module 2 was conducted at 2 sites in the United States.
Pre-assignment details
The screening period was of 30 days for both parts of the study. Informed Consent Form (ICF) was signed prior to screening procedures. All the study assessments were performed as per the schedule of assessment. Participants who met the eligibility criteria were randomized to study intervention in addition to receiving background local standard of care therapy.
Participants by arm
| Arm | Count |
|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID Participants received AZD4573 9 mg as Intravenous (IV) infusion once weekly with acalabrutinib 100 mg twice daily. | 9 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID Participants received AZD4573 dose expansion to RP2D 12 mg as IV infusion once weekly with acalabrutinib 100 mg twice daily. | 28 |
| Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID Participants received AZD4573 12 mg monotherapy until progression and thereafter received a combination regimen of AZD4573 12 mg once weekly and acalabrutinib 100 mg twice daily. | 3 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg | Ongoing subjects in Post Trial Access Program | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 2 Period 1 + 2: AZD4573 12 mg Monotherapy + Combination BID | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 11 Participants | 0 Participants | 13 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 17 Participants | 3 Participants | 27 Participants |
| Race/Ethnicity, Customized Asian | 2 Participants | 8 Participants | 0 Participants | 10 Participants |
| Race/Ethnicity, Customized Missing | 0 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Reported | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 6 Participants | 17 Participants | 2 Participants | 25 Participants |
| Sex: Female, Male Female | 4 Participants | 10 Participants | 0 Participants | 14 Participants |
| Sex: Female, Male Male | 5 Participants | 18 Participants | 3 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 4 / 9 | 16 / 28 | 0 / 3 |
| other Total, other adverse events | 9 / 9 | 28 / 28 | 3 / 3 |
| serious Total, serious adverse events | 4 / 9 | 16 / 28 | 2 / 3 |
Outcome results
Primary
Module 1: Number of Participants With Adverse Events
Safety and tolerability of AZD4573 in combination with acalabrutinib was assessed.
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The safety analysis set included all participants who received any amount of AZD4573 and/or acalabrutinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Number of Participants With Adverse Events | Any adverse event (AE) | 9 Participants |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Number of Participants With Adverse Events | Any serious adverse event (SAE) | 4 Participants |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Number of Participants With Adverse Events | Any adverse event (AE) | 28 Participants |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Number of Participants With Adverse Events | Any serious adverse event (SAE) | 16 Participants |
Primary
Module 1: Overall Response Rate (ORR) of AZD4573 in Combination With Acalabrutinib
Overall response rate (ORR), defined as the proportion of participants who have a tumour response (complete response \[CR\] and partial response \[PR\]).
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Overall Response Rate (ORR) of AZD4573 in Combination With Acalabrutinib | 44.4 Percentage of participants with response |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Overall Response Rate (ORR) of AZD4573 in Combination With Acalabrutinib | 50.0 Percentage of participants with response |
Primary
Module 2: Number of Participants With Adverse Events
Assessed safety and confirmed the RP2D of AZD4573 monotherapy in MCL participants and assessed the safety and tolerability of AZD4573 in combination with acalabrutinib in participants administered AZD4573 monotherapy.
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The safety analysis set included all participants who received any amount of AZD4573 and/or acalabrutinib.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 2: Number of Participants With Adverse Events | Any AE | 3 Participants |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 2: Number of Participants With Adverse Events | Any SAE | 1 Participants |
Secondary
Module 1: AUCinf of Acalabrutinib
Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUCinf of Acalabrutinib | Cycle 1 Week 1 Day 1 | 600.1 h*ng/mL | Geometric Coefficient of Variation 34.99 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUCinf of Acalabrutinib | Cycle 1 Week 1 Day 1 | 501.3 h*ng/mL | Geometric Coefficient of Variation 58.03 |
Secondary
Module 1: AUCinf of ACP-5862
Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUCinf of ACP-5862 | Cycle 1 Week 1 Day 1 | NA h*ng/mL | — |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUCinf of ACP-5862 | Cycle 1 Week 1 Day 1 | 935.2 h*ng/mL | Geometric Coefficient of Variation 38.81 |
Secondary
Module 1: AUCinf of AZD4573
Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 1 Week 1 Day 1 | NA h*ng/mL | — |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 1 Week 2 Day 1 | 1188 h*ng/mL | Geometric Coefficient of Variation 160.1 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 1 Week 3 Day 1 | 1588 h*ng/mL | Geometric Coefficient of Variation 169.6 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 2 Week 1 Day 1 | 4672 h*ng/mL | Geometric Coefficient of Variation 162.9 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 2 Week 1 Day 1 | 1853 h*ng/mL | Geometric Coefficient of Variation 29.55 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 1 Week 1 Day 1 | 640.5 h*ng/mL | Geometric Coefficient of Variation 15.33 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 1 Week 3 Day 1 | 1736 h*ng/mL | Geometric Coefficient of Variation 67.09 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUCinf of AZD4573 | Cycle 1 Week 2 Day 1 | 847.4 h*ng/mL | Geometric Coefficient of Variation 68.22 |
Secondary
Module 1: AUClast of Acalabrutinib
Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 1 Week 1 Day 1 | 493.9 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 58.91 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 1 Week 2 Day 1 | 520.9 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 46.04 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 1 Week 3 Day 1 | 475.9 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 45.57 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 2 Week 1 Day 1 | 481.8 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 58.39 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 2 Week 1 Day 1 | 424.5 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 162.8 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 1 Week 1 Day 1 | 631.4 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 69.98 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 1 Week 3 Day 1 | 570.7 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 67.75 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of Acalabrutinib | Cycle 1 Week 2 Day 1 | 638.2 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 81.66 |
Secondary
Module 1: AUClast of ACP-5862
Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 1 Week 1 Day 1 | 673.9 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 93.89 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 1 Week 2 Day 1 | 1173 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 48.03 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 1 Week 3 Day 1 | 1204 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 36.24 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 2 Week 1 Day 1 | 941.9 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 102.5 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 2 Week 1 Day 1 | 849.3 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 60.56 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 1 Week 1 Day 1 | 870.8 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 68.73 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 1 Week 3 Day 1 | 1093 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 54.5 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of ACP-5862 | Cycle 1 Week 2 Day 1 | 1135 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 54.95 |
Secondary
Module 1: AUClast of AZD4573
Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 1 Week 3 Day 1 | 1273 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 127.7 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 1 Week 2 Day 1 | 845.3 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 134.8 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 2 Week 1 Day 1 | 1939 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 330.9 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 1 Week 1 Day 1 | 532.9 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 164.5 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 1 Week 2 Day 1 | 929.0 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 55.85 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 1 Week 1 Day 1 | 561.3 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 60.83 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 2 Week 1 Day 1 | 1439 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 90.63 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: AUClast of AZD4573 | Cycle 1 Week 3 Day 1 | 1697 hours*nanogram per milliliter (h*ng/mL) | Geometric Coefficient of Variation 62.55 |
Secondary
Module 1: Cmax of Acalabrutinib
Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 1 Week 1 Day 1 | 219.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 66.94 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 1 Week 2 Day 1 | 209.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.79 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 1 Week 3 Day 1 | 232.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 74.77 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 2 Week 1 Day 1 | 217.5 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 100.8 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 2 Week 1 Day 1 | 256.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 67.75 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 1 Week 1 Day 1 | 306.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 76.06 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 1 Week 3 Day 1 | 274.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.98 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of Acalabrutinib | Cycle 1 Week 2 Day 1 | 322.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 95.53 |
Secondary
Module 1: Cmax of ACP-5862
Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 1 Week 3 Day 1 | 320.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 35.92 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 2 Week 1 Day 1 | 304.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 79.28 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 1 Week 1 Day 1 | 199.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 129.3 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 1 Week 2 Day 1 | 382.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 51.58 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 1 Week 2 Day 1 | 288.0 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 63.26 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 1 Week 3 Day 1 | 282.9 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 55.76 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 1 Week 1 Day 1 | 250.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 78.12 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of ACP-5862 | Cycle 2 Week 1 Day 1 | 251.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 45.54 |
Secondary
Module 1: Cmax of AZD4573
Maximum concentration that a drug achieves in a specified compartment or test area of the body after the drug has been administered (Cmax).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 1 Week 1 Day 1 | 164.2 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 469 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 1 Week 2 Day 1 | 235.7 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 359.3 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 1 Week 3 Day 1 | 337.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 194.3 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 2 Week 1 Day 1 | 643.1 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 578 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 2 Week 1 Day 1 | 294.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 48.83 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 1 Week 1 Day 1 | 112.6 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 70.2 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 1 Week 3 Day 1 | 270.8 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 38.61 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Cmax of AZD4573 | Cycle 1 Week 2 Day 1 | 185.3 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 50.61 |
Secondary
Module 1: Complete Response (CR) Rate
CR is defined as no detectable evidence of tumor, according to the revised response criteria for malignant lymphoma.
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Complete Response (CR) Rate | 11.1 Percentage of participants with response |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Complete Response (CR) Rate | 21.4 Percentage of participants with response |
Secondary
Module 1: Duration of Response (DoR)
DoR, defined as the time from the first objective response of CR or PR to the time of documented disease progression or death due to any cause, whichever occurs first.
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The response evaluable analysis set included participants dosed with AZD4573 or acalabrutinib with a baseline tumour assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Duration of Response (DoR) | 4.4 Months |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Duration of Response (DoR) | 3.3 Months |
Secondary
Module 1: Overall Survival (OS)
OS, defined as the time from first dose until the date of death from any cause.
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The full analysis set included all participants who received any amount of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Overall Survival (OS) | NA Months |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Overall Survival (OS) | 8.8 Months |
Secondary
Module 1: Progression Free Survival (PFS)
PFS, defined as the time from first dose date to documented disease progression, or death from any cause, whichever occurs first
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Population: The full analysis set included all participants who received any amount of study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Progression Free Survival (PFS) | 2.1 Months |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Progression Free Survival (PFS) | 2.8 Months |
Secondary
Module 1: t1/2 of Acalabrutinib
Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 1 Week 1 Day 1 | 1.332 Hours (h) | Geometric Coefficient of Variation 22.01 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 1 Week 2 Day 1 | 1.383 Hours (h) | Geometric Coefficient of Variation 49.15 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 1 Week 3 Day 1 | 1.238 Hours (h) | Geometric Coefficient of Variation 20.93 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 2 Week 1 Day 1 | NA Hours (h) | — |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 2 Week 1 Day 1 | 1.398 Hours (h) | Geometric Coefficient of Variation 32.2 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 1 Week 1 Day 1 | 1.108 Hours (h) | Geometric Coefficient of Variation 12.06 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 1 Week 3 Day 1 | 1.546 Hours (h) | Geometric Coefficient of Variation 38.08 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of Acalabrutinib | Cycle 1 Week 2 Day 1 | 1.274 Hours (h) | Geometric Coefficient of Variation 25.09 |
Secondary
Module 1: t1/2 of ACP-5862
Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 1 Week 3 Day 1 | 2.650 Hours (h) | Geometric Coefficient of Variation 34.68 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 1 Week 2 Day 1 | NA Hours (h) | — |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 1 Week 1 Day 1 | NA Hours (h) | — |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 2 Week 1 Day 1 | NA Hours (h) | — |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 1 Week 2 Day 1 | 3.021 Hours (h) | Geometric Coefficient of Variation 47.65 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 1 Week 1 Day 1 | 2.568 Hours (h) | Geometric Coefficient of Variation 33.27 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of ACP-5862 | Cycle 1 Week 3 Day 1 | 3.557 Hours (h) | Geometric Coefficient of Variation 38.06 |
Secondary
Module 1: t1/2 of AZD4573
Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 1 Week 1 Day 1 | NA Hours (h) | — |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 1 Week 2 Day 1 | 3.364 Hours (h) | Geometric Coefficient of Variation 43.8 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 1 Week 3 Day 1 | 4.465 Hours (h) | Geometric Coefficient of Variation 42.28 |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 2 Week 1 Day 1 | 6.508 Hours (h) | Geometric Coefficient of Variation 30.61 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 2 Week 1 Day 1 | 5.808 Hours (h) | Geometric Coefficient of Variation 25.52 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 1 Week 1 Day 1 | 3.692 Hours (h) | Geometric Coefficient of Variation 37.98 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 1 Week 3 Day 1 | 6.177 Hours (h) | Geometric Coefficient of Variation 30.16 |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: t1/2 of AZD4573 | Cycle 1 Week 2 Day 1 | 5.407 Hours (h) | Geometric Coefficient of Variation 73.47 |
Secondary
Module 1: Tmax of Acalabrutinib
Time to reach peak or maximum observed concentration following drug administration (tmax).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 1 Week 1 Day 1 | 1.242 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 1 Week 2 Day 1 | 2.017 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 1 Week 3 Day 1 | 1.233 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 2 Week 1 Day 1 | 1.933 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 2 Week 1 Day 1 | 1.200 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 1 Week 1 Day 1 | 1.117 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 1 Week 3 Day 1 | 1.433 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of Acalabrutinib | Cycle 1 Week 2 Day 1 | 1.133 Hours (h) |
Secondary
Module 1: Tmax of ACP-5862
Time to reach peak or maximum observed concentration following drug administration (tmax).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 1 Week 1 Day 1 | 3.067 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 1 Week 2 Day 1 | 2.075 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 1 Week 3 Day 1 | 1.233 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 2 Week 1 Day 1 | 2.167 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 1 Week 2 Day 1 | 2.117 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 1 Week 1 Day 1 | 1.117 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 1 Week 3 Day 1 | 1.892 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of ACP-5862 | Cycle 2 Week 1 Day 1 | 2.117 Hours (h) |
Secondary
Module 1: Tmax of AZD4573
Time to reach peak or maximum observed concentration following drug administration (tmax).
Time frame: Cycle 1 (5 weeks in total) on Day 1 of Week 1, 2 and 3, and Cycle 2 (3 weeks in total) on Day 1 of Week 1
Population: The pharmacokinetic analysis set included all dosed patients with reportable plasma concentrations and no important adverse events or protocol deviations that may impact PK.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 1 Week 1 Day 1 | 1.992 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 1 Week 2 Day 1 | 1.892 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 1 Week 3 Day 1 | 2.192 Hours (h) |
| Module 1 Part A: AZD4573 9 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 2 Week 1 Day 1 | 2.067 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 2 Week 1 Day 1 | 2.083 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 1 Week 1 Day 1 | 2.083 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 1 Week 3 Day 1 | 2.000 Hours (h) |
| Module 1 Part B: AZD4573 12 mg + 100g Acalabrutinib BID | Module 1: Tmax of AZD4573 | Cycle 1 Week 2 Day 1 | 2.033 Hours (h) |