Follicular Lymphoma Clinical Trial
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
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.
Status | Recruiting |
Enrollment | 206 |
Est. completion date | January 15, 2027 |
Est. primary completion date | January 15, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 130 Years |
Eligibility | 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. |
Country | Name | City | State |
---|---|---|---|
Australia | Research Site | Bedford Park | |
Australia | Research Site | Heidelberg | |
Australia | Research Site | Hobart | |
Australia | Research Site | Melbourne | |
Japan | Research Site | Chuo-ku | |
Japan | Research Site | Koto-ku | |
Japan | Research Site | Nagoya-shi | |
Japan | Research Site | Yamagata-shi | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Korea, Republic of | Research Site | Seoul | |
Taiwan | Research Site | Kaohsiung City | |
Taiwan | Research Site | Kweishan | |
Taiwan | Research Site | Tainan | |
Taiwan | Research Site | Taipei | |
United States | Research Site | Austin | Texas |
United States | Research Site | Charlotte | North Carolina |
United States | Research Site | Columbus | Ohio |
United States | Research Site | Houston | Texas |
United States | Research Site | Louisville | Kentucky |
United States | Research Site | Milwaukee | Wisconsin |
United States | Research Site | New Brunswick | New Jersey |
United States | Research Site | Pittsburgh | Pennsylvania |
United States | Research Site | Portland | Oregon |
United States | Research Site | Tampa | Florida |
Lead Sponsor | Collaborator |
---|---|
AstraZeneca |
United States, Australia, Japan, Korea, Republic of, Taiwan,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | |
Primary | 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 | |
Primary | Maximum Observed Serum Concentration of AZD0486 (Cmax) | The maximum observed serum concentration on a concentration time curve. | 4 weeks | |
Primary | 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 | |
Primary | 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 | Anti-Lymphoma Activity by Objective Response Rate (ORR) | Objective response rate is defined as the proportion of subjects with a confirmed partial or complete response to treatment | 48 months | |
Secondary | Anti-Lymphoma Activity by Progression-Free Survival (PFS) | Progression-free survival time is defined as the time from the first dose of AZD0486 to progression or death, whichever occurs first | 48 months | |
Secondary | Anti-Lymphoma Activity by Duration of Objective Response (DOR) | The duration of objective response for a subject is defined as the time from the initial objective response to disease progression or death, whichever occurs first | 48 months | |
Secondary | Anti-Lymphoma Activity by Clinical Benefit Rate | Clinical benefit rate is defined as the proportion of subjects with a confirmed complete response, partial response or minor response, or stable disease for at least 24 weeks after responding to treatment | 48 months |
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