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

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04594642
• Other study ID #: D7400C00006
• Status: Recruiting
• Phase: Phase 1
• Start date: March 2, 2021
• Est. completion date: January 15, 2027

Study information

• Verified date: May 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The study consists of 3 parts. Part 1 Arm A is a dose escalation study allowing the assessment of safety, tolerability, PK and PD profiles of single-agent AZD0486. Part 2 Arm B will evaluate the MTD (or RP2D) of AZD0486 monotherapy in subjects with biopsy proven RR DLBCL and HGBL. This will be initiated once expansion dose has been selected based on data from Part 1 Arm A. Part 2 Arm C evaluate the MTD (or RP2D) of AZD0486 monotherapy in subjects with biopsy proven RR FL. Arm C will be initiated once the expansion dose for FL has been selected based on data from the Monotherapy Dose Escalation (Part 1, Arm A). The expansion dose and dosing frequency for Part 2 will be chosen by the SMG based on safety, tolerability, and PK/PD data collected during the dose escalation portion of the study.

Recruitment information / eligibility

• 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.

Related Conditions & MeSH terms

• B-cell Non Hodgkin Lymphoma
• Diffuse Large B Cell Lymphoma
• Follicular Lymphoma
• High-grade B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Non-Hodgkin

Intervention

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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Australia,  Japan,  Korea, Republic of,  Taiwan, 

Outcome

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