B-cell Non Hodgkin LymphomaPhase 1NCT04594642
A Study of AZD0486 in Subjects With B-Cell Non-Hodgkin Lymphoma
A Phase 1 study testing AZD0486 IV in people with B-cell Non Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma, run by AstraZeneca at 25 sites in 5 countries.
Trial summary
This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with B-cell non-Hodgkin lymphoma (B-NHL). Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- B-cell Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma
- What is being tested?
- AZD0486 IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 226 participants
- Where
- 25 sitesin 5 countries
- Study dates
- 2 Mar 2021to 19 Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
- Relapsed/refractory cohorts:
- In order to be eligible subjects must have received at least 2 prior lines of therapy and not be candidates for treatment regimens known to provide clinical benefit in B-NHL. CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T cell therapies.
- 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria. Radiation to localized disease prior to study entry is allowed if >14 days from first dose.
- All Cohorts:
- Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
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- Subject must have adequate liver, bone marrow and kidney function (eGFR ≥ 50 mL/min).
- Subject must have locally confirmed CD19 positivity (must be documented after time of progression from last CD19-targeted therapy, if received)
- Subject must have at least 1 measurable disease site
- Subject must have ANC >/= 1000/mm3, platelets >/= 50,000 mm3, hemoglobin >/= 8.0 g/dL. Transfusion and/or growth factor are allowed but counts must be stable for at least 72 hours afterwards prior to screening
- Subject must have a total bilirubin <1.5x ULN, AST/ALT < 3xULN
Who cannot join
- Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
- Subject has active central nervous system (CNS) involvement by their B-NHL. --Subjects may be eligible with a distant history of CNS involvement that has been adequately treated with no evidence of recurrence within last 6 months from screening.
- Subject has a history of leukemic presentation of their B-NHL (>5,000 circulating lymphoma cells/uL in the peripheral blood).
- Subject has history or presence of clinically significant CNS pathology
- Subject has CNS involvement from active or history of autoimmune disease.
- Subject received CD19 CAR T therapy within 3 months prior to first dose.
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- Subject experienced Grade ≥ 3 cytokine release syndrome (CRS) following prior T-cell engager (TCE) or CAR T-cell therapy.
- Subject experienced Grade ≥ 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy.
- Subject has received a peripheral autologous stem cell transplant (SCT) within 12 weeks, or an allogeneic SCT within 1 year of the first dose of study drug treatment or has received an SCT and requires ongoing immunosuppressive therapy.
- Subjects with human immunodeficiency virus (HIV) infection, or subjects with chronic or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV). HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. Subjects with chronic HBV may be enrolled if the HBV viral load is undetectable on suppressive therapy, or if the subject has a documented cure. Subjects with HCV who have a documented cure may be enrolled.
- Subject has a history of major cardiac abnormalities.
- If female, subject must not be pregnant or breastfeeding.
Trial locations and contacts
25 sites in 5 countries.
25 sites in 5 countries
United States9 sites
Research Site
Austin, Texas, 78704
Research Site
Charlotte, North Carolina, 28204
Research Site
Columbus, Ohio, 43210
Research Site
Houston, Texas, 77030
Research Site
Louisville, Kentucky, 40207
Research Site
Milwaukee, Wisconsin, 53226
Research Site
New Brunswick, New Jersey, 08901
Research Site
Pittsburgh, Pennsylvania, 15237
Research Site
Tampa, Florida, 33612
South Korea5 sites
Research Site
Seoul, 03080
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Research Site
Seoul, 06591
Research Site
Seoul, 120-752
Japan4 sites
Research Site
Chūōku, 104-0045
Research Site
Kōtoku, 135-8550
Research Site
Nagoya, 460-0001
Research Site
Yamagata, 990-9585
Taiwan4 sites
Research Site
Kaohsiung City, 833401
Research Site
Kweishan, 333
Research Site
Tainan, 704
Research Site
Taipei, 10002
Australia3 sites
Research Site
Heidelberg, 3084
Research Site
Hobart, 7000
Research Site
Melbourne, 3004
About this study
Official title: A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects With B-Cell Non-Hodgkin Lymphoma
This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with B-cell non-Hodgkin lymphoma (B-NHL).
Read the detailed description
This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.
- Conditions
- B-cell Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma
- Being tested
- AZD0486 IV
- Keywords
- NHL, DLBCL, HGBL, CD19, FL
- Medical subject headings
- Lymphoma, B-Cell, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD0486 IVDrug
Also called TNB-486
AZD0486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells leading to T cell-mediated cytotoxicity of malignant B cells
| Study group | Role | What they receive |
|---|---|---|
| AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL | Experimental | AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. Depending on cohort, subjects may receive priming or step-up dosing administered weekly during cycle 1 before reaching the target dose. Additional cohorts may be opened where subjects receive weekly dosing during Cycles 1-2. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing Receives: Drug: AZD0486 IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of subjects with Dose-limiting toxicities (DLT)
A DLT is defined as a TEAE that is not unequivocally due to the subject's underlying malignancy or other extraneous cause. DLT evaluable subjects are defined as those subjects who receive either the target dose of AZD0486 or priming dose(s) in any step-up dose schedule and are assessed for toxicities for the 28-day evaluation period.
The NCI-CTCAE version 5.0 will be used (except for CRS and NT). A DLT will be evaluated as Non-hematologic, Hematologic, Cytokine Release Syndrome (CRS), or neurotoxicity.
Measured: 28 days
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
The incidence, timing, seriousness, and relationship to study treatment of adverse events will be evaluated.
Measured: From screening until 90 Days after end of treatment
Maximum Observed Serum Concentration of AZD0486 (Cmax)
The maximum observed serum concentration on a concentration time curve.
Measured: 4 Weeks
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Area under the serum concentration-time curve from time zero to time of last measurable concentration.
Measured: 4 Weeks
Apparent terminal half-life (t1/2) of AZD0486
Terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods.
Measured: From screening until 90 Days after end of treatment
Secondary outcomes (4)
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
Measured: 48 months
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Progression-free survival time is defined as the time from the first dose of AZD0486 to progression or death, whichever occurs first
Measured: 48 months
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
The duration of objective response for a subject is defined as the time from the initial objective response to disease progression or death, whichever occurs first
Measured: 48 months
Anti-Lymphoma Activity by Clinical Benefit Rate
Clinical benefit rate is defined as the proportion of subjects with a confirmed complete response, partial response or minor response, or stable disease for at least 24 weeks after responding to treatment
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2020
- Study start2 Mar 2021
- Primary completion19 Jun 2028 (estimated)
- Study completion19 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell 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
- Not applicable
- Intervention model
- Sequential
- Model description
- Adult subjects with B-NHL who will be enrolled into cohorts of incrementally increasing doses. Escalation is dependent upon ongoing review of emerging data by the Safety Monitoring Group (SMG).
- Masking
- None (open label)
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Sermer, MD, Study director, AstraZeneca
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04594642
- Sponsor's protocol ID
- D7400C00006
- Status last verified
- Sep 2026
- First submitted
- 13 Oct 2020
- Last updated
- 25 Sep 2026
- Results posted
- No
- 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 Vivli.org. 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 approved. Supporting
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects With B-Cell Non-Hodgkin Lymphoma
- ClinicalTrials.gov ID
- NCT04594642
- Acronym / sponsor ID
- D7400C00006
- Conditions
- B-cell Non Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, High-grade B-cell Lymphoma, Follicular Lymphoma
- Keywords
- NHL, DLBCL, HGBL, CD19, FL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 226 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 2 Mar 2021 (actual)
- Primary completion
- 19 Jun 2028 (estimated)
- Study completion
- 19 Jun 2028 (estimated)
- First posted
- 20 Oct 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging bispecific antibody, in subjects with B-cell non-Hodgkin lymphoma (B-NHL).
Detailed description
This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Adult subjects with B-NHL who will be enrolled into cohorts of incrementally increasing doses. Escalation is dependent upon ongoing review of emerging data by the Safety Monitoring Group (SMG).
| Arm | Type | Receives |
|---|---|---|
| AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL | Experimental | Drug: AZD0486 IVAZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. Depending on cohort, subjects may receive priming or step-up dosing administered weekly during cycle 1 before reaching the target dose. Additional cohorts may be opened where subjects receive weekly dosing during Cycles 1-2. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
- Relapsed/refractory cohorts:
- In order to be eligible subjects must have received at least 2 prior lines of therapy and not be candidates for treatment regimens known to provide clinical benefit in B-NHL. CAR T-naive subjects are allowed if they have declined, are considered ineligible for, or do not have timely access to CAR T cell therapies.
- 1L FL cohorts: Subject has biopsy-proven FL Grade 1-3a per WHO 2016 classification, Stage II-IV, FL International Prognostic Index 2-5 that has not been treated with prior systemic lymphoma-directed therapy and requires initiation of treatment based on GELF criteria. Radiation to localized disease prior to study entry is allowed if >14 days from first dose.
- All Cohorts:
Key exclusion criteria (12 listed)
- Subject has been diagnosed with or treated for another malignancy whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
- Subject has active central nervous system (CNS) involvement by their B-NHL. --Subjects may be eligible with a distant history of CNS involvement that has been adequately treated with no evidence of recurrence within last 6 months from screening.
- Subject has a history of leukemic presentation of their B-NHL (>5,000 circulating lymphoma cells/uL in the peripheral blood).
- Subject has history or presence of clinically significant CNS pathology
- Subject has CNS involvement from active or history of autoimmune disease.
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 |
|---|---|---|
| AZD0486 IVAlso: TNB-486AZD0486 is a bispecific antibody targeting CD19 on tumor cells and CD3 on T-cells leading to T cell-mediated cytotoxicity of malignant B cells | Drug | AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL |
Primary outcome
Incidence of subjects with Dose-limiting toxicities (DLT)
Time frame: 28 days
A DLT is defined as a TEAE that is not unequivocally due to the subject's underlying malignancy or other extraneous cause. DLT evaluable subjects are defined as those subjects who receive either the target dose of AZD0486 or priming dose(s) in any step-up dose schedule and are assessed for toxicities for the 28-day evaluation period. The NCI-CTCAE version 5.0 will be used (except for CRS and NT). A DLT will be evaluated as Non-hematologic, Hematologic, Cytokine Release Syndrome (CRS), or neurotoxicity.
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
Time frame: From screening until 90 Days after end of treatment
The incidence, timing, seriousness, and relationship to study treatment of adverse events will be evaluated.
Maximum Observed Serum Concentration of AZD0486 (Cmax)
Time frame: 4 Weeks
The maximum observed serum concentration on a concentration time curve.
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Time frame: 4 Weeks
Area under the serum concentration-time curve from time zero to time of last measurable concentration.
Apparent terminal half-life (t1/2) of AZD0486
Time frame: From screening until 90 Days after end of treatment
Terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods.
4 secondary outcomes
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Time frame: 48 months
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Time frame: 48 months
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Time frame: 48 months
Anti-Lymphoma Activity by Clinical Benefit Rate
Time frame: 48 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- 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 Vivli.org. 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 approved. Supporting
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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.
David Sermer, MD study director
AstraZeneca
25 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AZD0486 IV in people with B-cell Non Hodgkin Lymphoma and Diffuse Large B Cell Lymphoma, run by AstraZeneca at 25 sites in 5 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 11 inclusion and 12 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: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, South Korea, Japan, Taiwan, Australia. 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?
This study is still under way. Results are not available in the source record yet.
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?
Incidence of subjects with Dose-limiting toxicities (DLT) (time frame: 28 days). The study lists 5 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 25 Sep 2026.