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

NCT ID: NCT04594642

Last Updated: 2025-11-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

317 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-02

Study Completion Date

2028-04-19

Brief Summary

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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

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

Conditions

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B-cell Non Hodgkin Lymphoma Diffuse Large B Cell Lymphoma High-grade B-cell Lymphoma Follicular Lymphoma

Keywords

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NHL DLBCL HGBL CD19 FL

Study Design

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Allocation Method

NA

Intervention Model

SEQUENTIAL

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).
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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

Group Type EXPERIMENTAL

AZD0486 IV

Intervention Type DRUG

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

Interventions

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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

Intervention Type DRUG

Other Intervention Names

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TNB-486

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

130 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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AstraZeneca

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Sermer, MD

Role: STUDY_DIRECTOR

AstraZeneca

Locations

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Research Site

Tampa, Florida, United States

Site Status RECRUITING

Research Site

Louisville, Kentucky, United States

Site Status RECRUITING

Research Site

New Brunswick, New Jersey, United States

Site Status RECRUITING

Research Site

Charlotte, North Carolina, United States

Site Status RECRUITING

Research Site

Columbus, Ohio, United States

Site Status RECRUITING

Research Site

Portland, Oregon, United States

Site Status WITHDRAWN

Research Site

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Research Site

Austin, Texas, United States

Site Status RECRUITING

Research Site

Houston, Texas, United States

Site Status RECRUITING

Research Site

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Research Site

Bedford Park, , Australia

Site Status NOT_YET_RECRUITING

Research Site

Heidelberg, , Australia

Site Status RECRUITING

Research Site

Hobart, , Australia

Site Status RECRUITING

Research Site

Melbourne, , Australia

Site Status RECRUITING

Research Site

Chūōku, , Japan

Site Status RECRUITING

Research Site

Kōtoku, , Japan

Site Status RECRUITING

Research Site

Nagoya, , Japan

Site Status RECRUITING

Research Site

Yamagata, , Japan

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Seoul, , South Korea

Site Status RECRUITING

Research Site

Kaohsiung City, , Taiwan

Site Status RECRUITING

Research Site

Kweishan, , Taiwan

Site Status RECRUITING

Research Site

Tainan, , Taiwan

Site Status RECRUITING

Research Site

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States Australia Japan South Korea Taiwan

Central Contacts

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AstraZeneca Clinical Study Information Center

Role: CONTACT

Phone: 1-877-240-9479

Email: [email protected]

Other Identifiers

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D7400C00006

Identifier Type: -

Identifier Source: org_study_id