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

Study identifier:D7400C00006

ClinicalTrials.gov identifier:NCT04594642

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects with Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

Medical condition

B-cell Non Hodgkin Lymphoma

Phase

Phase 1

Healthy volunteers

Study drug

AZD0486 IV

Sex

All

Estimated Enrollment

116

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 02 Mar 2021

Estimated Primary Completion Date: 15 Jan 2027

Estimated Study Completion Date: 15 Jan 2027

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Oct 2024 by AstraZeneca

Collaborators

N/A

Inclusion and exclusion criteria

Inclusion Criteria

- Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
-. In order to be eligible for this study subjects must 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.
- 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.
-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.

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Arms	Assigned Interventions
Experimental: AZD0486 Monotherapy Dose Escalation in Subjects with RR 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 during cycle 1 before reaching the target dose. 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 Name: TNB-486

Arms

Assigned Interventions

Experimental: AZD0486 Monotherapy Dose Escalation in Subjects with RR 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 during cycle 1 before reaching the target dose. 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 Name: TNB-486

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

David Sermer

AstraZeneca