Clinical Trials List
Protocol NumberD7400C00006
NCT Number(ClinicalTrials.gov Identfier)NCT04594642
Active
2023-10-20 - 2026-12-31
Phase I
Recruiting4
A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AZD0486, a Bispecific Antibody Targeting CD19 in Subjects With B-Cell Non-Hodgkin Lymphoma
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Trial Applicant
Syneos Health
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Sponsor
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Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 林明恩 Division of Hematology & Oncology
- - - Division of Hematology & Oncology
- Chieh-Lung Cheng Division of Hematology & Oncology
- Chien-Chin Lin Division of Hematology & Oncology
- Tai-Chung Huang Division of Hematology & Oncology
- MING YAO Division of Hematology & Oncology
- CHENG-HONG TSAI Division of Hematology & Oncology
- 田豐銘 Division of Hematology & Oncology
- HSIN-AN HOU Division of Hematology & Oncology
- Huai-Hsuan Huang Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Ming-Chung Kao Division of Hematology & Oncology
- Tung-Liang Lin Division of Hematology & Oncology
- HSUAN JEN SHIH Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Tsai-Yun Chen
Co-Principal Investigator
- 傅蓓安 Division of Hematology & Oncology
- 顏志傑 Division of Hematology & Oncology
- Ya-Ping Chen Division of Hematology & Oncology
- Ya-Ting Hsu Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
B-cell Non Hodgkin Lymphoma、Diffuse Large B Cell Lymphoma
Objectives
Primary:
• Evaluate the safety and tolerability of AZD0486 as a monotherapy.
• Confirm the maximum tolerated dose (MTD) and/or recommended dose (RP2D) of AZD0486 as a monotherapy.
• Evaluate the pharmacokinetics (PK) of AZD0486 as a monotherapy.
Secondary:
• Evaluate the clinical activity of AZD0486 as a monotherapy.
• Evaluate the anti-antibody titer of AZD0486 as a monotherapy.
Exploratory:
• Evaluate pharmacodynamics and exploratory biomarkers, and assess their correlation with safety, pharmacokinetics, and clinical activity.
Test Drug
靜脈輸注液
Active Ingredient
MURINE MONOCLONAL ANTIBODY CD3 (MUROMONAL CD3)
Dosage Form
246
Dosage
MG
Endpoints
Trial follow-up visits and assessments will be conducted on days 1, 8, and 15 of the screening period and each cycle, according to the event timeline. For a 4-week cycle, additional trial follow-up visits and assessments will be conducted on days 2, 3, 8, 9, 10, 15, 16, 17, and 22 of cycle 1, and day 2 of cycle 6.
Assessments will be conducted before all investigational drug administration, at the end-of-treatment (EOT) follow-up visit (within 30 days after the last dose of investigational drug), and 90 (± 7) days after the last dose of investigational drug, including physical examination, hematological and chemical tests. Positron emission tomography-computed tomography (PET-CT) will be performed on day 1 of every three cycles. If a subject has a history of bone marrow involvement, bone marrow biopsy and aspiration should be performed whenever possible to confirm any complete response (CR) and assess minimal residual disease (MRD) in subjects who achieve an objective response. Adverse events, medications used, laboratory data, and vital signs will be assessed throughout the trial. In addition, participants will be contacted every 12 weeks to collect survival data.
Assessments will be conducted before all investigational drug administration, at the end-of-treatment (EOT) follow-up visit (within 30 days after the last dose of investigational drug), and 90 (± 7) days after the last dose of investigational drug, including physical examination, hematological and chemical tests. Positron emission tomography-computed tomography (PET-CT) will be performed on day 1 of every three cycles. If a subject has a history of bone marrow involvement, bone marrow biopsy and aspiration should be performed whenever possible to confirm any complete response (CR) and assess minimal residual disease (MRD) in subjects who achieve an objective response. Adverse events, medications used, laboratory data, and vital signs will be assessed throughout the trial. In addition, participants will be contacted every 12 weeks to collect survival data.
Inclution Criteria
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
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
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.
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.
The Estimated Number of Participants
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Taiwan
20 participants
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Global
231 participants
