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

NCT04594642 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D7400C00006
• Study Type: interventional
• Target: 227
• Locations: 5 countries
• Sites: 27

Brief 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).

Conditions

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

Keywords

NHL; DLBCL; HGBL; CD19; FL

Outcome Measures

Primary Outcomes (5)

• 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.

  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.

  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.

  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.

  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.

  From screening until 90 Days after end of treatment

Secondary Outcomes (4)

• Anti-Lymphoma Activity by Objective Response Rate (ORR)

  48 months

• Anti-Lymphoma Activity by Progression-Free Survival (PFS)

  48 months

• Anti-Lymphoma Activity by Duration of Objective Response (DOR)

  48 months

• Anti-Lymphoma Activity by Clinical Benefit Rate

  48 months

Study Arms (1)

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

Drug: AZD0486 IV

Interventions

AZD0486 IV 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

Also known as: TNB-486

AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL

Eligibility Criteria

• Age: 18 Years - 130 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• L 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (27)

Research Site

Tampa, Florida, 33612, United States

RECRUITING

Research Site

Louisville, Kentucky, 40207, United States

RECRUITING

Research Site

New Brunswick, New Jersey, 08901, United States

RECRUITING

Research Site

Charlotte, North Carolina, 28204, United States

RECRUITING

Research Site

Columbus, Ohio, 43210, United States

RECRUITING

Research Site

Portland, Oregon, 97239, United States

WITHDRAWN

Research Site

Pittsburgh, Pennsylvania, 15237, United States

RECRUITING

Research Site

Austin, Texas, 78704, United States

RECRUITING

Research Site

Houston, Texas, 77030, United States

RECRUITING

Research Site

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Research Site

Bedford Park, 5042, Australia

WITHDRAWN

Research Site

Heidelberg, 3084, Australia

RECRUITING

Research Site

Hobart, 7000, Australia

RECRUITING

Research Site

Melbourne, 3004, Australia

RECRUITING

Research Site

Chūōku, 104-0045, Japan

RECRUITING

Research Site

Kōtoku, 135-8550, Japan

RECRUITING

Research Site

Nagoya, 460-0001, Japan

RECRUITING

Research Site

Yamagata, 990-9585, Japan

RECRUITING

Research Site

Seoul, 03080, South Korea

RECRUITING

Research Site

Seoul, 05505, South Korea

RECRUITING

Research Site

Seoul, 06351, South Korea

RECRUITING

Research Site

Seoul, 06591, South Korea

RECRUITING

Research Site

Seoul, 120-752, South Korea

RECRUITING

Research Site

Kaohsiung City, 833401, Taiwan

RECRUITING

Research Site

Kweishan, 333, Taiwan

RECRUITING

Research Site

Tainan, 704, Taiwan

RECRUITING

Research Site

Taipei, 10002, Taiwan

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• David Sermer, MD

  AstraZeneca

  STUDY DIRECTOR

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 13, 2020
• First Posted: October 20, 2020
• Study Start: March 2, 2021
• Primary Completion (Estimated): April 19, 2028
• Study Completion (Estimated): April 19, 2028
• Last Updated: April 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• 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:
• 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.

Locations

KR (5); AU (4); US (10); TW (4); JP (4)