Non-Hodgkin LymphomaPhase 1NCT05205161
A Phase I/II Study of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Advanced Non-Hodgkin Lymphoma
A Phase 1 study testing AZD0466 in people with Non-Hodgkin Lymphoma, run by AstraZeneca at 10 sites in 7 countries.
Trial summary
This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Non-Hodgkin Lymphoma
- What is being tested?
- AZD0466
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 10 sitesin 7 countries
- Study dates
- 5 Jul 2022to 17 Aug 2023
- Phase
- Phase 1
- 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
- Patient must be aged ≥ 18 years at the time of signing the informed consent. In some countries, parental consent may be required in addition to an assent form for patients who are 18 years of age.
- Patient must have histologically documented diagnosis of B-cell non-Hodgkin lymphoma (B-NHL) as defined by a B-cell neoplasm in the World Health Organisation classification scheme except as noted in the exclusion criteria.
- Patient has relapsed after or failed to respond to at least 2 but no more than 5 prior systemic treatment regimens (including investigational therapy) and for whom there is no available therapy expected to improve survival (eg, standard chemotherapy, autologous stem cell transplantation (SCT), chimeric antigen receptor T cell (CAR-T) cell therapy).
- Documented active disease requiring treatment that is relapsed or refractory defined as:
- Recurrence/relapse of disease after response to prior line(s) of therapy.
- Progressive disease (refractory) on/after completion of the treatment regimen preceding entry into the study.
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- Must have at least one measurable, fluorodeoxyglucose positron emission tomography (FDG-PET) avid lesion (except for MZL), based on bi-dimensional assessment on PET and computed tomography (CT)/magnetic resonance imaging (MRI) scan. A measurable lesion is defined as:
- For nodal lesions: longest diameter > 1.5 cm
- For extranodal lesions: longest diameter > 1 cm
- Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2. Performance status must not have deteriorated by ≥ 2 levels within 2 weeks after providing informed consent.
- Adequate haematologic, hepatic, and renal function
- Adequate cardiac function as demonstrated by left ventricular ejection fraction > 50% on screening cardiac multigated acquisition, magnetic resonance imaging, or echocardiogram.
- Women of childbearing potential and men should use protocol defined contraceptive measures.
- Willing and able to participate in all required study evaluations and procedures including receiving IV administration of study intervention and admission to the hospital, when required, for administration of study treatment and monitoring.
- All patients must be willing to undergo an incisional or excisional lymph node or tissue biopsy or to provide a lymph node or tissue biopsy from the most recent available archival tissue.
- For inclusion in the genetic component of the study, patients must fulfil protocol defined criteria.
- Additional Inclusion Criteria for Cohort B1 (R/R mantle cell lymphoma [MCL]):
- Histologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1, as assessed by Investigator or local pathologist.
- Must have relapsed after or failed to respond to at least 2 prior lines of treatment, including one anti-CD20 monoclonal antibody (mAb) and a Bruton's tyrosine kinase inhibitor.
- Additional Inclusion Criteria for Cohort B2 (R/R FL or MZL):
- Histologically confirmed diagnosis of FL Grade 1, 2, or 3a OR histologically confirmed MZL including splenic, nodal, and extranodal subtypes, as assessed by Investigator or local pathologist.
- For FL patients: Previously received at least 2 prior systemic treatment regimens (including anti-CD20 mAb and an alkylating agent).
- For MZL patients: Previously received at least 2 prior lines of systemic therapy including at least one anti-CD20 mAb-directed regimen either as monotherapy or as chemoimmunotherapy (Helicobacter pylori eradication and radiation therapy alone will not be considered a systemic treatment regimen).
- Additional Inclusion Criteria for Cohort B3 (R/R DLBCL):
- Histologically confirmed DLBCL (including transformed FL) OR FL Grade 3b.
- Must have received 2 lines of systemic therapy including at least one anti-CD20 mAb-directed regimen and must have failed or are ineligible for stem cell transplantation (if indicated per local institutional guidelines).
Who cannot join
- Diagnosis of post-transplant lymphoproliferative disease, Richter's transformation, Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukaemia, chronic lymphocytic leukaemia, small lymphocytic lymphoma.
- High risk of TLS according to Howard modification of Cairo-Bishop criteria and/or the presence of bulky disease.
- Unresolved toxicity from prior anticancer therapy. Patients with Grade 2 neuropathy or Grade 2 alopecia are eligible.
- Active idiopathic thrombocytopenic purpura.
- Active central nervous system (CNS) involvement by lymphoma, leptomeningeal disease or spinal cord compression.
- Known history of infection with human immunodeficiency virus.
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- Known serologic status reflecting active hepatitis B or C infection; concurrent infection with cytomegalovirus (CMV).
- Patients must be tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and those with active infection in accordance with local testing guidelines will be excluded.
- Any evidence of severe or uncontrolled systemic diseases; current unstable or uncompensated respiratory or cardiac conditions; uncontrolled hypertension; history of, or active, bleeding diatheses; uncontrolled active systemic fungal, bacterial, or other infection.
- Any of the following cardiac criteria at screening: patients with a history of myocarditis within one year of study entry, or heart failure; mean resting corrected QT interval (QTcF) ≥ 470 msec obtained from 3 electrocardiograms (ECGs), in the absence of a cardiac pacemaker; any factors that increase the risk of QTc prolongation or risk of arrhythmic events; any clinically important abnormalities in rhythm, conduction or morphology of resting ECG.
- History of another life-threatening malignancy ≤ 2 years prior to first dose of study intervention.
- Any of the following currently or in the 6 months prior to the first dose of study intervention: 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 following: radiotherapy less than 2 weeks prior to the first dose of study intervention; any investigational agents or study drugs from a previous clinical study within ≤ 14 days or 5 half-lives prior to the first dose of study intervention; any other chemotherapy, immunotherapy, immunosuppressant medication or anticancer agents within 21 days of the first dose of study intervention; Prior allogenic haematopoietic stem cell transplantation (HSCT) within 6 months from the first dose of study intervention (patients > 6 months after allogenic HSCT are eligible in the absence of active graft-versus host disease and concomitant immune-suppressive therapy). Eligible patients must have stopped immunosuppression at least 2 months prior to study entry; prior cellular therapies such as CAR-T and/or autologous HSCT within 3 months prior to the first dose of study intervention; major surgery ≤ 21 days, or minor surgical procedures ≤ 7 days, prior to the first dose of study intervention; 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 cytochrome 3A (CYP3A) inhibitors, which cannot be discontinued within 5 half-lives of the first dose of study intervention 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 12 days of the drug prior to the first dose of study intervention and withheld until 14 days after the last dose of AZD0466; concurrent anticoagulation therapy, including aspirin, which cannot be stopped; medications with known risk of Torsades de Pointes within 5 half-lives of the first dose of study intervention and continuing until 5 half-lives after the last dose of AZD0466.
- Administration of a live, attenuated vaccine within 4 weeks before first dose of study intervention.
- Administration of inactivated vaccines or protein/RNA immunogen vaccines.
- Patients with a known hypersensitivity to polyethylene glycol, pegylated products, or drugs with a similar chemical structure or class to AZD0466 or other BH3 mimetic.
- Additional Exclusion Criteria for Cohort B1:
- Patients with known blastoid or pleiomorphic variant at study entry/most recent relapse.
- Additional Exclusion Criteria for Cohort B2:
- Histologically confirmed diagnosis of FL grade 3B.
- Known transformation to aggressive lymphoma, eg, large cell lymphoma.
Trial locations and contacts
10 sites in 7 countries.
10 sites in 7 countries
Spain3 sites
Research Site
Palma de Mallorca, 07010
Research Site
Pamplona, 31008
Research Site
Salamanca, 37007
About this study
Official title: A Modular Phase I/II, Open-label, Dose Escalation and Expansion, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Patients With Advanced Non-Hodgkin Lymphoma.
This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL
Read the detailed description
This is a modular Phase I/II, open-label, dose escalation and expansion, multicentre Study. The study consists of individual modules, each evaluating the safety and tolerability of AZD0466 as monotherapy or with a specific combination treatment. The initial components are the core protocol, which contains information applicable to all modules, and Module 1.
Module 1 will evaluate the safety, tolerability, PK, and preliminary efficacy of AZD0466 monotherapy and will include 2 parts. Part A dose escalation and Part B dose expansion cohorts. Part A will enrol patients with advanced B-NHL and once the RP2D has been determined, Part B may open to further explore the preliminary anticancer efficacy of AZD0466 monotherapy in patients with selected lymphoid malignancies.
Part A: Phase 1 dose setting to assess the safety and tolerability and determine dose(s) and schedule(s) to be evaluated in Part B.
Part B: Phase 1b/2a dose expansion to assess the efficacy of AZD0466 in 3 select patient populations: relapsed/refractory (R/R) mantle cell lymphoma (MCL) (Cohort B1), R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) (Cohort B2), and R/R diffuse large B-cell lymphoma (DLBCL) (Cohort B3).
- Conditions
- Non-Hodgkin Lymphoma
- Being tested
- AZD0466
- Keywords
- Open-label,, Dose Escalation, Dose Expansion,, Multicentre Study, Anticancer, Pegylated poly-L-lysine dendrimer
- Medical subject headings
- Lymphoma, Non-Hodgkin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0466Drug
All patients will receive treatment with the investigational product AZD0466 via intravenous infusion.
| Study group | Role | What they receive |
|---|---|---|
| Part A (Dose Escalation): Dose Level (DL)-1 | Experimental | Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part A (Dose Escalation): DL1 | Experimental | Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part A (Dose Escalation): DL2 | Experimental | Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part A (Dose Escalation): DL3 | Experimental | Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part A (Dose Escalation): DL4 | Experimental | Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part B (Dose Expansion): Cohort B1 (R/R MCL) | Experimental | Participants with advanced R/R MCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part B (Dose Expansion): Cohort B2 (R/R FL or MZL) | Experimental | Participants with advanced R/R FL or MZL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
| Part B (Dose Expansion): Cohort B3 (R/R DLBCL) | Experimental | Participants with advanced R/R DLBCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. Receives: Drug: AZD0466 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events (AE)
The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.
Measured: Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
Number of Participants With Dose Limiting Toxicity (DLT)
The DLT of AZD0466 in participants with R/R B-NHL was evaluated.
Measured: Day 1 to end of Cycle 1 (28 days treatment cycle)
Secondary outcomes (12)
Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320
The Cmax of AZD4320 was assessed to characterise the pharmacokinetic (PK) profile of AZD0466.
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320
The tmax of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320
The λz of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Measured: Cycle 1 Day 8 (Study Day 8), Cycle 2 Day 1 (Study Day 22)
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320
The t1/2λz of AZD4320 was assessed to characterise Pk profile of AZD0466.
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320
The AUC0-24 of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (AUC0-72) of AZD4320
The AUC0-72 of AZD4320 was assessed to characterise the Pk profile of AZD0466.
Measured: Cycle 1 Day 8
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320
The AUClast of AZD4320 was assessed to characterise the Pk profile of AZD0466
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320
The tlast of AZD4320 was assessed to characterise the Pk profile of AZD0466
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Concentration Prior to Dosing (Ctrough) of AZD4320
The Ctrough of AZD4320 was assessed to characterise the Pk profile of AZD0466
Measured: Cycle 2 Day 1
Part A:Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Analyte Concentration Divided by the Dose Administered (Dose Normalised AUClast) of AZD4320
The Dose normalised AUClast of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (Dose Normalised AUC0-72) of AZD4320
The Dose normalised AUC0-72 of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Measured: Cycle 1 Day 8
Part A: Maximum Observed Plasma (Peak) Drug Concentration Divided by the Dose Administered (Dose Normalised Cmax) of AZD4320
The Dose normalised Cmax of total AZD4320 was assessed to characterise the Pk profile of AZD0466
Measured: Cycle 1 Day 8, Cycle 2 Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2022
- Study start5 Jul 2022
- Primary completion17 Aug 2023
- Study completion17 Aug 2023
Why it stopped: Due to safety reasons.
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 Non-Hodgkin LymphomaStudies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05205161
- Sponsor's protocol ID
- D8242C00001
- Other IDs
- 2021-003410-39
- Status last verified
- Nov 2024
- First submitted
- 5 Jan 2022
- Last updated
- 7 Jan 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- 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 requests 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 7 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Modular Phase I/II, Open-label, Dose Escalation and Expansion, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of AZD0466 as Monotherapy or in Combination With Anticancer Agents in Patients With Advanced Non-Hodgkin Lymphoma.
- ClinicalTrials.gov ID
- NCT05205161
- Acronym / sponsor ID
- D8242C00001
- Conditions
- Non-Hodgkin Lymphoma
- Keywords
- Open-label,, Dose Escalation, Dose Expansion,, Multicentre Study, Anticancer, Pegylated poly-L-lysine dendrimer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to safety reasons.
- Enrolment
- 7 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 5 Jul 2022 (actual)
- Primary completion
- 17 Aug 2023 (actual)
- Study completion
- 17 Aug 2023 (actual)
- First posted
- 25 Jan 2022 (actual)
- Results
- Posted 7 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates the safety, tolerability, PK, and preliminary efficacy of AZD0466 as monotherapy or in combination with other anticancer agents in patients with advanced NHL
Detailed description
This is a modular Phase I/II, open-label, dose escalation and expansion, multicentre Study. The study consists of individual modules, each evaluating the safety and tolerability of AZD0466 as monotherapy or with a specific combination treatment. The initial components are the core protocol, which contains information applicable to all modules, and Module 1.
Module 1 will evaluate the safety, tolerability, PK, and preliminary efficacy of AZD0466 monotherapy and will include 2 parts. Part A dose escalation and Part B dose expansion cohorts. Part A will enrol patients with advanced B-NHL and once the RP2D has been determined, Part B may open to further explore the preliminary anticancer efficacy of AZD0466 monotherapy in patients with selected lymphoid malignancies.
Part A: Phase 1 dose setting to assess the safety and tolerability and determine dose(s) and schedule(s) to be evaluated in Part B.
Part B: Phase 1b/2a dose expansion to assess the efficacy of AZD0466 in 3 select patient populations: relapsed/refractory (R/R) mantle cell lymphoma (MCL) (Cohort B1), R/R follicular lymphoma (FL) or marginal zone lymphoma (MZL) (Cohort B2), and R/R diffuse large B-cell lymphoma (DLBCL) (Cohort B3).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part A (Dose Escalation): Dose Level (DL)-1 | Experimental | Drug: AZD0466Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part A (Dose Escalation): DL1 | Experimental | Drug: AZD0466Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part A (Dose Escalation): DL2 | Experimental | Drug: AZD0466Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part A (Dose Escalation): DL3 | Experimental | Drug: AZD0466Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part A (Dose Escalation): DL4 | Experimental | Drug: AZD0466Participants with advanced R/R B-NHL will receive AZD0466 on day 1 , day 4, day 8 day 15, day 22 of cycle 1 and day 1, day 8 day 15, day 22 of cycle 2 and beyond until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part B (Dose Expansion): Cohort B1 (R/R MCL) | Experimental | Drug: AZD0466Participants with advanced R/R MCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part B (Dose Expansion): Cohort B2 (R/R FL or MZL) | Experimental | Drug: AZD0466Participants with advanced R/R FL or MZL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
| Part B (Dose Expansion): Cohort B3 (R/R DLBCL) | Experimental | Drug: AZD0466Participants with advanced R/R DLBCL will receive AZD0466 at the recommended phase 2 dose (RP2D) until maximum 2 years or until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study intervention, whichever occurs first. |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (26 listed)
- Patient must be aged ≥ 18 years at the time of signing the informed consent. In some countries, parental consent may be required in addition to an assent form for patients who are 18 years of age.
- Patient must have histologically documented diagnosis of B-cell non-Hodgkin lymphoma (B-NHL) as defined by a B-cell neoplasm in the World Health Organisation classification scheme except as noted in the exclusion criteria.
- Patient has relapsed after or failed to respond to at least 2 but no more than 5 prior systemic treatment regimens (including investigational therapy) and for whom there is no available therapy expected to improve survival (eg, standard chemotherapy, autologous stem cell transplantation (SCT), chimeric antigen receptor T cell (CAR-T) cell therapy).
- Documented active disease requiring treatment that is relapsed or refractory defined as:
- Must have at least one measurable, fluorodeoxyglucose positron emission tomography (FDG-PET) avid lesion (except for MZL), based on bi-dimensional assessment on PET and computed tomography (CT)/magnetic resonance imaging (MRI) scan. A measurable lesion is defined as:
Key exclusion criteria (21 listed)
- Diagnosis of post-transplant lymphoproliferative disease, Richter's transformation, Burkitt's lymphoma, Burkitt-like lymphoma, lymphoblastic lymphoma/leukaemia, chronic lymphocytic leukaemia, small lymphocytic lymphoma.
- High risk of TLS according to Howard modification of Cairo-Bishop criteria and/or the presence of bulky disease.
- Unresolved toxicity from prior anticancer therapy. Patients with Grade 2 neuropathy or Grade 2 alopecia are eligible.
- Active idiopathic thrombocytopenic purpura.
- Active central nervous system (CNS) involvement by lymphoma, leptomeningeal disease or spinal cord compression.
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 |
|---|---|---|
| AZD0466All patients will receive treatment with the investigational product AZD0466 via intravenous infusion. | Drug | Part A (Dose Escalation): DL1, Part A (Dose Escalation): DL2, Part A (Dose Escalation): DL3, Part A (Dose Escalation): DL4, Part A (Dose Escalation): Dose Level (DL)-1, Part B (Dose Expansion): Cohort B1 (R/R MCL), Part B (Dose Expansion): Cohort B2 (R/R FL or MZL), Part B (Dose Expansion): Cohort B3 (R/R DLBCL) |
Primary outcome
Number of Participants With Adverse Events (AE)
Time frame: Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month
The safety and the tolerability of AZD0466 in patients with relapsed/ refractory B-cell non-Hodgkin lymphoma (R/R B-NHL) was evaluated.
Number of Participants With Dose Limiting Toxicity (DLT)
Time frame: Day 1 to end of Cycle 1 (28 days treatment cycle)
The DLT of AZD0466 in participants with R/R B-NHL was evaluated.
12 secondary outcomes
Part A: Maximum Observed Plasma (Peak) Drug Concentration (Cmax) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Time to Reach Peak or Maximum Observed Concentration or Response Following Drug Administration (Tmax) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Terminal Rate Constant, Estimated by Log-linear Least Squares Regression of the Terminal Part of the Concentration-time Curve (λz) of AZD4320
Time frame: Cycle 1 Day 8 (Study Day 8), Cycle 2 Day 1 (Study Day 22)
Part A: Half-life Associated With Terminal Slope (λz) of a Semi-logarithmic Concentration-time Curve (t1/2λz) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours After the Start of Infusion (AUC0-24) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Partial Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (AUC0-72) of AZD4320
Time frame: Cycle 1 Day 8
Part A: Area Under the Plasma Concentration-curve From Time 0 to the Last Quantifiable Concentration (AUClast) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Time of Last Observed (Quantifiable) Concentration (Tlast) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Concentration Prior to Dosing (Ctrough) of AZD4320
Time frame: Cycle 2 Day 1
Part A:Area Under the Plasma Concentration-time Curve From Time 0 to Time of Last Quantifiable Analyte Concentration Divided by the Dose Administered (Dose Normalised AUClast) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Part A: Area Under the Plasma Concentration-time Curve From Time 0 to 72 Hours After the Start of Infusion (Dose Normalised AUC0-72) of AZD4320
Time frame: Cycle 1 Day 8
Part A: Maximum Observed Plasma (Peak) Drug Concentration Divided by the Dose Administered (Dose Normalised Cmax) of AZD4320
Time frame: Cycle 1 Day 8, Cycle 2 Day 1
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- D8242C00001\_CSP\_RedactedLink provided by the sponsor.
- D8242C00001\_CSR Synopsis\_RedactedLink provided by the sponsor.
- D8242C00001\_SAP\_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 requests 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.
10 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD0466 in people with Non-Hodgkin Lymphoma, run by AstraZeneca at 10 sites in 7 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 21 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: stopped early, as of the sponsor's last update on 7 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Spain, South Korea, United States, Australia, France and 2 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 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.
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 7 Jan 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?
Number of Participants With Adverse Events (AE) (time frame: Day 1 to Follow-up (30 days post last dose or up to the day prior to start of subsequent cancer therapy) up to approximately 1 year 1 month). The study lists 2 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 7 Jan 2025.