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

JRCT ID: jRCT2041230077

Registered date:05/09/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: B-Cell Non-Hodgkin Lymphoma
• Date of first enrollment: 12/09/2023
• Target sample size: 9
• Countries of recruitment: US,Japan,South Korea,Japan,Australia,Japan
• Study type: Interventional
• Intervention(s): AZD0486 is administered single-agent once every 2 weeks (Q2W). In the Japan cohorts, the first 3 subjects will receive a AZD0486 target dose of 7200 micro g in a double SUD approach. Cycle 1 Days 1 (270 micro g) and 8 (1000 micro g), prior to the target dose on Day 15 (7200 micro g). Dosing will continue thereafter Q2W on Days 1 and 15, in 28-day cycles. AZD0486 may continue for up to two years of treatment or until the criteria for discontinuation are met.

Outcome(s)

Primary Outcome

Activity: The activity endpoints include objective response rate (ORR, defined as CR + PR), clinical benefit rate (CBR; defined as CR + PR + MR + SD for 24 weeks), overall survival (OS), progression-free survival (PFS), time to progression (TTP), time to response (TTR), and duration of objective response (DOR).
Pharmacokinetic: Concentrations of AZD0486 and antidrug antibody (ADA) will be determined at designated time points throughout the study. Values for the PK parameters of AZD0486 including the Cmax, the time to Cmax (Tmax), AUC from time 0 to the time of the last measurable concentration (AUCt), clearance (CL), the terminal phase elimination rate constant, and terminal half-life (t1/2,) will be determined after infusion in Cycle 1 using non-compartmental methods.
Exploratory Research Variables: Exploratory research will be conducted to study exposure-response relationships via biomarker relationships with PK, safety, and clinical activity.
Safety: Adverse events, laboratory profiles, physical exams, and vital signs will be assessed throughout the study. Adverse events will be graded according to the NCI CTCAE, version 5.0.
Adverse events will be collected until the 90-day post-last treatment visit or until a new line of therapy is initiated, whichever occurs earlier.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 80age old
• Gender: Both

Include 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).

Exclude 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 a 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 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.

Related Information

• Primary Sponsor: Misaki Masako
• Secondary ID(s): NCT04594642