What side effects are associated with this type of intervention?

Common treatments for Non-Hodgkin's Lymphoma, such as CD19 x CD3 T-cell engaging bispecific antibodies, often have side effects related to immune system activation. These can include cytokine release syndrome (CRS), which manifests as fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing. Other potential side effects include infusion-related reactions, which may cause symptoms like chills, fever, and allergic reactions. Additionally, patients may experience hematologic toxicities such as neutropenia, anemia, and thrombocytopenia, increasing the risk of infections and bleeding. Monitoring and managing these side effects are crucial for patient safety.

What prior FDA approvals exist?

The FDA has approved several treatments for Non-Hodgkin's Lymphoma (NHL) that target CD19 or involve T-cell engagement. Notably, CAR-T cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are CD19-directed treatments that have shown efficacy in relapsed or refractory cases of NHL. These therapies involve modifying a patient's T-cells to target CD19 on B-cells, similar to the mechanism of action of AZD0486. Both axi-cel and tisa-cel have received accelerated approval for use in adults with relapsed or refractory NHL after two or more lines of systemic therapy.

What other types of research exist?

Promising, novel alternatives to AZD0486 for Non-Hodgkin's Lymphoma patients include: 1) CAR T-cell therapies such as axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah), which have shown significant efficacy in relapsed or refractory B-cell NHL. 2) Bispecific antibodies like glofitamab and epcoritamab, which target CD20 and CD3, offering a different mechanism of action compared to AZD0486. 3) Antibody-drug conjugates such as polatuzumab vedotin, which targets CD79b and delivers cytotoxic agents directly to cancer cells. These therapies represent cutting-edge advancements and provide additional options for patients who may not respond to or tolerate AZD0486.

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CAR T-cell Therapy

AZD0486 for Non-Hodgkin's Lymphoma

Phase 1

Recruiting

Research Sponsored by Teneobio, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2

Must not have

Subject experienced Grade ≥ 2 neurotoxicity/immune effector cell-associated neurotoxicity syndrome (ICANS) following prior TCE or CAR T-cell therapy

Subject has a history of major cardiac abnormalities

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment for patients with a type of lymphoma that hasn't responded to other treatments. The treatment works by connecting immune cells to cancer cells, helping the immune system destroy the cancer. This approach is innovative and promising in the treatment of malignant lymphoma.

Who is the study for?

This trial is for adults with B-cell non-Hodgkin lymphoma that's come back or didn't respond after at least two treatments. They should be fairly active (ECOG ≤ 2), have good liver, bone marrow, and kidney function, and not be suitable for other effective therapies. Pregnant or breastfeeding women can't join.

What is being tested?

The study tests AZD0486 IV, a new type of drug aiming to engage immune T-cells against cancer cells in patients with specific types of relapsed or refractory B-cell lymphomas who've tried multiple previous therapies.

What are the potential side effects?

Potential side effects may include severe immune reactions like cytokine release syndrome (CRS) and neurotoxicity similar to those seen in other T-cell engaging therapies. The exact side effects of AZD0486 are being studied.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with a type of non-Hodgkin lymphoma.

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I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I had a severe reaction to previous T-cell therapy.

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I have a history of serious heart problems.

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I am not pregnant or breastfeeding.

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I had a severe reaction to previous immune cell therapy.

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I have or had another cancer that might affect this treatment's safety or results.

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My B-cell non-Hodgkin lymphoma has affected my brain or spinal cord.

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My B-cell non-Hodgkin lymphoma presented as leukemia.

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I have a significant brain or nerve condition.

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I have or had an autoimmune disease affecting my brain or spinal cord.

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I had a stem cell transplant recently or am on immunosuppressive therapy after one.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and 48 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Apparent terminal half-life (t1/2) of AZD0486

Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast)

Incidence of subjects with Dose-limiting toxicities (DLT)

+2 more

Secondary study objectives

Anti-Lymphoma Activity by Clinical Benefit Rate

Anti-Lymphoma Activity by Duration of Objective Response (DOR)

Anti-Lymphoma Activity by Objective Response Rate (ORR)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: AZD0486 Monotherapy Dose Escalation in Subjects with RR B-NHLExperimental Treatment1 Intervention

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

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include monoclonal antibodies, chimeric antigen receptor T-cell (CAR-T) therapy, and bispecific T-cell engagers like AZD0486. Monoclonal antibodies, such as rituximab, target specific antigens like CD20 on B-cells, marking them for destruction by the immune system. CAR-T therapy involves modifying a patient's T-cells to express receptors specific to antigens on lymphoma cells, such as CD19, enabling direct targeting and killing of these cells. Bispecific T-cell engagers, like AZD0486, simultaneously bind to CD19 on B-cells and CD3 on T-cells, bringing them into close proximity to facilitate the T-cell-mediated killing of the cancer cells. These targeted therapies are crucial for NHL patients as they offer more precise and effective treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.