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

Description

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 relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) who have received 2 or more prior lines of therapy.This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.

Trial Eligibility

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.

Study Info

Interventions

Locations Recruiting

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