Advanced Haematological MalignanciesPhase 1/2NCT04630756
AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Blood Cancer
A Phase 1/2 study testing AZD4573 and Acalabrutinib in people with Advanced Haematological Malignancies, run by AstraZeneca at 17 sites in 9 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Advanced Haematological Malignancies
- What is being tested?
- AZD4573 and Acalabrutinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 17 sitesin 9 countries
- Study dates
- 17 Feb 2021to 27 Feb 2025
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- Uric acid level < upper limit of normal (ULN).
- 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.
- 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.
Who cannot join
- 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).
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- 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.
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, stomach resection, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, bowel obstruction, or gastric restrictions and bariatric surgery.
- Prior use of standard anti-lymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment.
- Requires treatment with strong CYP3A inhibitors or inducers.
- Requires treatment with proton-pump inhibitors. Participants receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrolment to this study.
- Serologic status reflecting active hepatitis B or C infection.
- Active Cytomegalovirus (CMV) infection.
- Requires or receiving therapeutic anticoagulants, with the exception of short-acting heparins, within 7 days of first dose of study treatment. Novel oral anticoagulants are allowed except for the initial high dose treatment period.
- Participants on dual antiplatelet and therapeutic anticoagulant therapy.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
- History of or ongoing confirmed progressive multifocal leukoencephalopathy
- Current refractory nausea and vomiting, malabsorption syndrome, disease significantly affecting gastrointestinal function, stomach resection, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery.
- Prior use of standard anti-lymphoma therapy or radiation therapy within 14 days of receiving the first dose of study treatment.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists.
- Requires treatment with strong CYP3A inhibitors or inducers.
- Requires treatment with proton-pump inhibitors. Participants receiving proton-pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrolment to this study.
- Serologic status reflecting active hepatitis B or C infection.
- Active CMV infection.
- Requires or receiving therapeutic anticoagulants, with the exception of short-acting heparins, within 7 days of first dose of study treatment. Novel oral anticoagulants are allowed except for the initial high dose treatment period.
- Participants on dual antiplatelet and therapeutic anticoagulant therapy.
- History of or ongoing confirmed progressive multifocal leukoencephalopathy
Trial locations and contacts
17 sites in 9 countries.
17 sites in 9 countries
United States4 sites
Research Site
Duarte, California, 91010
Research Site
Houston, Texas, 77030
Research Site
La Jolla, California, 92093-0052
Research Site
Salt Lake City, Utah, 84112
South Korea3 sites
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Spain2 sites
Research Site
Barcelona, 08035
Research Site
Palma de Mallorca, 07120
About this study
Official title: A Modular Phase I/II, Open-label, Multicentre Study to Assess AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Haematological Malignancies
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.
Read the 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.
- Conditions
- Advanced Haematological Malignancies
- Being tested
- AZD4573, Acalabrutinib
- Keywords
- AZD4573, Anti-cancer Agents, Sequential dose-setting and expansion treatment
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD4573Drug
Also called AZ13810325
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).
AcalabrutinibDrug
Also called ACP-196 /Calquence
Oral Acalabrutinib capsule will be administered twice daily continuously from Day 1 of Cycle 1 Week 1 in combination with AZD4573.
| Study group | Role | What they receive |
|---|---|---|
| Module 1: Part A and Part B | Experimental | Participants will receive intravenous ascending doses of AZD4573 once weekly with oral acalabrutinib twice daily continuously in Part A. For Part A, cohorts 1, 2, and 3 have different target dose levels respectively.
In Part B, participants will receive the RP2D of AZD4573 from Part A. Receives: Drug: AZD4573; Drug: Acalabrutinib |
| Module 2: Part A and Part B | Experimental | Participants will receive AZD4573 as monotherapy for Period 1 and AZD4573 + acalabrutinib as combination therapy for Period 2.
Part B of Module 2 will be determined from the data emerging from Part A. Receives: Drug: AZD4573; Drug: Acalabrutinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Module 1: Number of Participants With Adverse Events
Safety and tolerability of AZD4573 in combination with acalabrutinib was assessed.
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
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.
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
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]).
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Secondary outcomes (19)
Module 1: Complete Response (CR) Rate
CR is defined as no detectable evidence of tumor, according to the revised response criteria for malignant lymphoma.
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
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.
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
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
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Module 1: Overall Survival (OS)
OS, defined as the time from first dose until the date of death from any cause.
Measured: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
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).
Measured: 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
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).
Measured: 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
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).
Measured: 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
Module 1: AUClast of AZD4573
Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).
Measured: 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
Module 1: AUClast of Acalabrutinib
Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).
Measured: 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
Module 1: AUClast of ACP-5862
Area under the plasma concentration time curve from zero to the time of the last measurable concentration (AUClast).
Measured: 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
Module 1: AUCinf of AZD4573
Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).
Measured: 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
Module 1: AUCinf of Acalabrutinib
Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).
Measured: 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
Module 1: AUCinf of ACP-5862
Area under the plasma concentration time curve from zero extrapolated to infinity (AUCinf).
Measured: 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
Module 1: Tmax of AZD4573
Time to reach peak or maximum observed concentration following drug administration (tmax).
Measured: 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
Module 1: Tmax of Acalabrutinib
Time to reach peak or maximum observed concentration following drug administration (tmax).
Measured: 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
Module 1: Tmax of ACP-5862
Time to reach peak or maximum observed concentration following drug administration (tmax).
Measured: 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
Module 1: t1/2 of AZD4573
Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).
Measured: 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
Module 1: t1/2 of Acalabrutinib
Time taken for half the initial dose of drug administered to be eliminated from the body (t1/2).
Measured: 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
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).
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Nov 2020
- Study start17 Feb 2021
- Primary completion8 Sep 2023
- Study completion27 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced Haematological MalignanciesStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Parexel
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04630756
- Sponsor's protocol ID
- D8230C00002
- Other IDs
- 2020-001642-18
- Status last verified
- Mar 2025
- First submitted
- 2 Sep 2020
- Last updated
- 9 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Modular Phase I/II, Open-label, Multicentre Study to Assess AZD4573 in Novel Combinations With Anti-cancer Agents in Patients With Advanced Haematological Malignancies
- ClinicalTrials.gov ID
- NCT04630756
- Acronym / sponsor ID
- D8230C00002
- Conditions
- Advanced Haematological Malignancies
- Keywords
- AZD4573, Anti-cancer Agents, Sequential dose-setting and expansion treatment
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Collaborators
- Parexel
- Study start
- 17 Feb 2021 (actual)
- Primary completion
- 8 Sep 2023 (actual)
- Study completion
- 27 Feb 2025 (actual)
- First posted
- 16 Nov 2020 (actual)
- Results
- Posted 21 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Module 1: Part A and Part B | Experimental | Drug: AZD4573, Drug: AcalabrutinibParticipants will receive intravenous ascending doses of AZD4573 once weekly with oral acalabrutinib twice daily continuously in Part A. For Part A, cohorts 1, 2, and 3 have different target dose levels respectively. In Part B, participants will receive the RP2D of AZD4573 from Part A. |
| Module 2: Part A and Part B | Experimental | Drug: AZD4573, Drug: AcalabrutinibParticipants will receive AZD4573 as monotherapy for Period 1 and AZD4573 + acalabrutinib as combination therapy for Period 2. Part B of Module 2 will be determined from the data emerging from Part A. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- 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.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD4573Also: AZ13810325AZD4573 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). | Drug | Module 1: Part A and Part B, Module 2: Part A and Part B |
| AcalabrutinibAlso: ACP-196 /CalquenceOral Acalabrutinib capsule will be administered twice daily continuously from Day 1 of Cycle 1 Week 1 in combination with AZD4573. | Drug | Module 1: Part A and Part B, Module 2: Part A and Part B |
Primary outcome
Module 1: Number of Participants With Adverse Events
Time frame: 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 2: Number of Participants With Adverse Events
Time frame: 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.
Module 1: Overall Response Rate (ORR) of AZD4573 in Combination With Acalabrutinib
Time frame: 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]).
19 secondary outcomes
Module 1: Complete Response (CR) Rate
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Module 1: Duration of Response (DoR)
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Module 1: Progression Free Survival (PFS)
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Module 1: Overall Survival (OS)
Time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)
Module 1: Cmax of AZD4573
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
Module 1: Cmax of Acalabrutinib
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
Module 1: Cmax of ACP-5862
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
Module 1: AUClast of AZD4573
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
Module 1: AUClast of Acalabrutinib
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
Module 1: AUClast of ACP-5862
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
Module 1: AUCinf of AZD4573
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
Module 1: AUCinf of Acalabrutinib
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
Module 1: AUCinf of ACP-5862
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
Module 1: Tmax of AZD4573
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
Module 1: Tmax of Acalabrutinib
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
Module 1: Tmax of ACP-5862
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
Module 1: t1/2 of AZD4573
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
Module 1: t1/2 of Acalabrutinib
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
Module 1: t1/2 of ACP-5862
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- D8230C00002\_CSP\_redactedLink provided by the sponsor.
- D8230C00002\_CSR Synopsis\_redactedLink provided by the sponsor.
- D8230C00002\_Statistical Analysis Plan\_redactedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
17 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD4573 and Acalabrutinib in people with Advanced Haematological Malignancies, run by AstraZeneca at 17 sites in 9 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 26 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, South Korea, Australia, Ireland, Spain and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Module 1: Number of Participants With Adverse Events (time frame: From Screening (Day -30 to Day -1) until disease progression or survival until death (approximately 2.5 years)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2025.