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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04594642




Registration number
NCT04594642
Ethics application status
Date submitted
13/10/2020
Date registered
20/10/2020
Date last updated
30/10/2024

Titles & IDs
Public title
A Study of AZD0486 in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
Scientific 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
Secondary ID [1] 0 0
D7400C00006
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Non Hodgkin Lymphoma 0 0
Diffuse Large B Cell Lymphoma 0 0
High-grade B-cell Lymphoma 0 0
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - AZD0486 IV

Experimental: AZD0486 Monotherapy Dose Escalation in Subjects with RR B-NHL - AZD0486 monotherapy will be administered intravenously on day 1 and 15 of 28 day cycles for a maximum of 2 years or until discontinuation criteria are met. 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: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence of subjects with Dose-limiting toxicities (DLT)
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Incidence of subjects with adverse events (AEs) and/or serious adverse events (SAEs)
Timepoint [2] 0 0
From screening until 90 Days after end of treatment
Primary outcome [3] 0 0
Maximum Observed Serum Concentration of AZD0486 (Cmax)
Timepoint [3] 0 0
4 Weeks
Primary outcome [4] 0 0
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)
Timepoint [4] 0 0
4 Weeks
Primary outcome [5] 0 0
Apparent terminal half-life (t1/2) of AZD0486
Timepoint [5] 0 0
From screening until 90 Days after end of treatment
Secondary outcome [1] 0 0
Anti-Lymphoma Activity by Objective Response Rate (ORR)
Timepoint [1] 0 0
48 months
Secondary outcome [2] 0 0
Anti-Lymphoma Activity by Progression-Free Survival (PFS)
Timepoint [2] 0 0
48 months
Secondary outcome [3] 0 0
Anti-Lymphoma Activity by Duration of Objective Response (DOR)
Timepoint [3] 0 0
48 months
Secondary outcome [4] 0 0
Anti-Lymphoma Activity by Clinical Benefit Rate
Timepoint [4] 0 0
48 months

Eligibility
Key inclusion criteria
* Biopsy proven B-NHL, including DLBCL, HGBL, or FL.

-. In order to be eligible for this study subjects must 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.
* 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
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.
* 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
2/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/01/2027
Actual
Sample size
Target
116
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Bedford Park
Recruitment hospital [2] 0 0
Research Site - Heidelberg
Recruitment hospital [3] 0 0
Research Site - Hobart
Recruitment hospital [4] 0 0
Research Site - Melbourne
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3084 - Heidelberg
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
New Jersey
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Pennsylvania
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin
Country [10] 0 0
Japan
State/province [10] 0 0
Chuo-ku
Country [11] 0 0
Japan
State/province [11] 0 0
Koto-ku
Country [12] 0 0
Japan
State/province [12] 0 0
Nagoya-shi
Country [13] 0 0
Japan
State/province [13] 0 0
Yamagata-shi
Country [14] 0 0
Korea, Republic of
State/province [14] 0 0
Seoul
Country [15] 0 0
Taiwan
State/province [15] 0 0
Kaohsiung City
Country [16] 0 0
Taiwan
State/province [16] 0 0
Kweishan
Country [17] 0 0
Taiwan
State/province [17] 0 0
Tainan
Country [18] 0 0
Taiwan
State/province [18] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/study/NCT04594642
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
David Sermer, MD
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
AstraZeneca Clinical Study Information Center
Address 0 0
Country 0 0
Phone 0 0
1-877-240-9479
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04594642