A Study of AZD0486 in Subjects With B-Cell Non-Hodgkin Lymphoma

April 28, 2026 updated by: AstraZeneca

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.

Study Type

Interventional

Enrollment (Estimated)

227

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Bedford Park, Australia, 5042
        • Withdrawn
        • Research Site
      • Heidelberg, Australia, 3084
        • Recruiting
        • Research Site
      • Hobart, Australia, 7000
        • Recruiting
        • Research Site
      • Melbourne, Australia, 3004
        • Recruiting
        • Research Site
  • Japan
      • Chūōku, Japan, 104-0045
        • Recruiting
        • Research Site
      • Kōtoku, Japan, 135-8550
        • Recruiting
        • Research Site
      • Nagoya, Japan, 460-0001
        • Recruiting
        • Research Site
      • Yamagata, Japan, 990-9585
        • Recruiting
        • Research Site
  • South Korea
      • Seoul, South Korea, 03080
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06351
        • Recruiting
        • Research Site
      • Seoul, South Korea, 05505
        • Recruiting
        • Research Site
      • Seoul, South Korea, 06591
        • Recruiting
        • Research Site
      • Seoul, South Korea, 120-752
        • Recruiting
        • Research Site
  • Taiwan
      • Kaohsiung City, Taiwan, 833401
        • Recruiting
        • Research Site
      • Kweishan, Taiwan, 333
        • Recruiting
        • Research Site
      • Tainan, Taiwan, 704
        • Recruiting
        • Research Site
      • Taipei, Taiwan, 10002
        • Recruiting
        • Research Site
  • United States
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • Research Site
    • Kentucky
      • Louisville, Kentucky, United States, 40207
        • Recruiting
        • Research Site
    • New Jersey
      • New Brunswick, New Jersey, United States, 08901
        • Recruiting
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28204
        • Recruiting
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Recruiting
        • Research Site
    • Oregon
      • Portland, Oregon, United States, 97239
        • Withdrawn
        • Research Site
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15237
        • Recruiting
        • Research Site
    • Texas
      • Austin, Texas, United States, 78704
        • Recruiting
        • Research Site
      • Houston, Texas, United States, 77030
        • Recruiting
        • Research Site
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 76 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

  • 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

Exclusion Criteria:

  • 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.
  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL
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
Drug: AZD0486 IV
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
Other Names:
  • TNB-486

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
28 days
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.
From screening until 90 Days after end of treatment
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.
From screening until 90 Days after end of treatment
Maximum Observed Serum Concentration of AZD0486 (Cmax)
Time Frame: 4 Weeks
The maximum observed serum concentration on a concentration time curve.
4 Weeks
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.
4 Weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Time Frame: 48 months
Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment
48 months
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Time Frame: 48 months
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
48 months
Anti-Lymphoma Activity by Clinical Benefit Rate
Time Frame: 48 months
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
48 months
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Time Frame: 48 months
Progression-free survival time is defined as the time from the first dose of AZD0486 to progression or death, whichever occurs first
48 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

AstraZeneca

Investigators

  • Study Director: David Sermer, MD, AstraZeneca

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 2, 2021

Primary Completion (Estimated)

April 19, 2028

Study Completion (Estimated)

April 19, 2028

Study Registration Dates

First Submitted

October 13, 2020

First Submitted That Met QC Criteria

October 13, 2020

First Posted (Actual)

October 20, 2020

Study Record Updates

Last Update Posted (Actual)

April 29, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D7400C00006

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

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

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Access Criteria:

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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