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

AstraZeneca logo

AstraZeneca

Status and phase

Enrolling
Phase 1

Conditions

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

Treatments

Drug: AZD0486 IV

Study type

Interventional

Funder types

Industry

Identifiers

NCT04594642
D7400C00006

Details and patient eligibility

About

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.

Full 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.

Enrollment

206 estimated patients

Sex

All

Ages

18 to 130 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

206 participants in 3 patient groups

Part 1, Arm A: AZD0486 Monotherapy Dose Escalation in Subjects with RR B-NHL
Experimental group
Description:
AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 24 cycles or until disease progression. Depending on cohort, subjects may receive priming or step-up dosing during cycle 1 before reaching the target dose. While on study, subjects will be monitored for safety and efficacy with periodic disease assessment with PET/CT. If subject achieves two consecutive CRs after completing C6, then they may be eligible for monthly dosing
Treatment:
Drug: AZD0486 IV
Part 2, Arm B: Monotherapy Dose Expansion in Subjects with RR DLBCL/HGBL
Experimental group
Description:
An expansion cohort in subjects with DLBCL or HGBL will be enrolled after RP2D is established.
Treatment:
Drug: AZD0486 IV
Part 2, Arm C: Monotherapy Dose Expansion in Subjects with RR FL
Experimental group
Description:
An expansion cohort in subjects with FL will be enrolled after RP2D is established.
Treatment:
Drug: AZD0486 IV

Trial contacts and locations

29

Loading...

Central trial contact

AstraZeneca Clinical Study Information Center

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems