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, Diffuse Large B Cell 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: 22 Jan 2027

Estimated Study Completion Date: 22 Jan 2027

Study design

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

Verification:

Verified 01 Mar 2024 by AstraZeneca

Collaborators

N/A

Inclusion and exclusion criteria

Inclusion Criteria

- Biopsy proven B-NHL, including DLBCL, HGBL, or FL.
-For Arm B Only: Subject has biopsy proven DLBCL or HGBL
-For Arm C only: Subject has biopsy proven FL
-Subject has received at least 2 lines of therapy to which the subject has been either refractory or has subsequently relapsed. In order to be eligible for this study subjects must not be candidates for treatment regimens known to provide clinical benefit in B-NHL.
-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 a history of central nervous system (CNS) involvement by their B-NHL
-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 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: Part 1, Arm A: 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 24 cycles or until disease progression. 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
Experimental: Part 2, Arm B: Monotherapy Dose Expansion in Subjects with RR DLBCL/HGBL An expansion cohort in subjects with DLBCL or HGBL will be enrolled after RP2D is established.	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
Experimental: Part 2, Arm C: Monotherapy Dose Expansion in Subjects with RR FL An expansion cohort in subjects with FL will be enrolled after RP2D is established.	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

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]

Investigators

Principal Investigator

David Sermer

AstraZeneca