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

PHASE1RECRUITING

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.

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Study details:

This dose escalation and optimization study, is evaluating the safety, tolerability, PK, PD and clinical activity of AZD0486 monotherapy.

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Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

Biopsy proven B-NHL, including DLBCL, HGBL, or FL.

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 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.

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Eligibility

Age eligible for study : 18 and older

Healthy volunteers accepted : No

Gender eligible for study: All

Things to know

Study dates

Study start: 2021-03-02

Primary completion: 2027-01-15

Study completion finish: 2027-01-15

Study type

TREATMENT

Phase

PHASE1

Trial ID

NCT04594642

Intervention or treatment

DRUG: AZD0486 IV

Conditions

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

Image related to Diffuse Large B Cell Lymphoma

Condition: Diffuse Large B Cell Lymphoma, Follicular Lymphoma and more
DRUG: AZD0486 IV
Bedford Park, Not Specified, Australia and more
Sponsor: AstraZeneca

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial? If you're a clinic or sponsor, you can claim this study. Claim or learn more.

Find a site

Closest Location:

Research Site

Research sites nearby

Select from list below to view details:

Research Site
Bedford Park, Not Specified, Australia
Research Site
Heidelberg, Not Specified, Australia
Research Site
Hobart, Not Specified, Australia
Research Site
Melbourne, Not Specified, Australia

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/Arm	Intervention/Treatment
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	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

Participant Group/Arm

Intervention/Treatment

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

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

What is the study measuring?

Primary outcome

Primary Outcome Measure	Primary Outcome Description	Primary Outcome Time Frame
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
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
Maximum Observed Serum Concentration of AZD0486 (Cmax)	The maximum observed serum concentration on a concentration time curve.	4 Weeks
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
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 outcome

Secondary Outcome Measure	Secondary Outcome Description	Secondary Outcome Time Frame
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
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
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
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

Frequently Asked Questions

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References

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