AZD0486 for Non-Hodgkin's Lymphoma

Recruiting at 37 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Teneobio, Inc.

Disqualifiers: Other malignancy, Active CNS involvement, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years

317 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AZD0486 (also known as TNB-486, a type of bispecific antibody) for individuals with B-cell non-Hodgkin lymphoma (B-NHL). The goal is to determine the treatment's safety and its effects in the body. Participants receive the medication through an IV, and researchers monitor for side effects and effectiveness against cancer. Suitable candidates have B-NHL that has returned or not responded to previous treatments and have not used certain other therapies. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that AZD0486 is likely to be safe for humans?

Research shows that AZD0486, also known as TNB-486, holds promise for safety in treating B-cell non-Hodgkin's lymphoma. Previous studies found that this bispecific antibody (a protein that can attach to two different targets) was well-tolerated by patients with difficult-to-treat forms of this cancer.

These studies reported manageable side effects, though specific details remain limited. The phase 1 trial aims to further explore its safety and patient tolerance, indicating early evidence of its safety for human testing.

While more information is needed to fully understand its safety, current evidence encourages those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about AZD0486 for non-Hodgkin's lymphoma because it represents a new approach in targeting cancer cells. Unlike standard treatments like chemotherapy and radiation that broadly attack fast-growing cells, AZD0486 is a monoclonal antibody designed to specifically target and bind to cancer cells, potentially reducing damage to healthy cells. It's administered intravenously, with a unique dosing schedule that allows for initial priming or step-up dosing, which could enhance its effectiveness and reduce side effects. This targeted approach offers hope for better outcomes and fewer side effects compared to traditional therapies.

What evidence suggests that AZD0486 might be an effective treatment for non-Hodgkin's lymphoma?

Research has shown that AZD0486, also known as TNB-486, could be beneficial in treating B-cell non-Hodgkin lymphoma (B-NHL). This treatment is a unique antibody that can simultaneously attach to two targets: CD19, found on certain cancer cells, and CD3, found on T-cells, a type of immune cell. In animal studies, TNB-486 effectively eliminated cancer cells when combined with human immune cells. This trial will evaluate AZD0486 monotherapy in participants with B-NHL. These findings suggest that AZD0486 might enhance the immune system's ability to combat B-NHL in humans. ^{1 2 3 5 6}

Who Is on the Research Team?

David Sermer, MD

Principal Investigator

AstraZeneca

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

My liver, bone marrow, and kidneys are functioning well.

I have a biopsy confirming I have follicular lymphoma.

I have had at least 2 treatments for my cancer but they didn't work or my cancer came back.

Exclusion Criteria

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

I have a history of serious heart problems.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

AZD0486 monotherapy administered intravenously on day 1 and 15 of 28-day cycles for up to 2 years

Up to 2 years

Bi-weekly visits (in-person) during cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Long-term follow-up

Monitoring of progression-free survival and other outcomes

48 months

What Are the Treatments Tested in This Trial?

Interventions

• TNB-486

Trial Overview 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.

How Is the Trial Designed?

Group I: AZD0486 Monotherapy Dose Escalation in Subjects with B-NHL Experimental Treatment 1 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 administered weekly during cycle 1 before reaching the target dose. Additional cohorts may be opened where subjects receive weekly dosing during Cycles 1-2. 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

Who Is Running the Clinical Trial?

Teneobio, Inc.

Lead Sponsor

Trials

4

Recruited

490+

AstraZeneca

Lead Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

TeneoTwo Inc.

Lead Sponsor

Trials

1

Recruited

230+

Published Research Related to This Trial

Chimeric anti-CD20 monoclonal antibodies (MAbs) have shown promising results in treating B cell non-Hodgkin's lymphoma (NHL), leading to increased global use of these therapies over the past five years.

These anti-CD20 MAbs can be used effectively either alone or in combination with traditional chemotherapy, particularly in consolidating remission after high-dose chemotherapy and stem cell rescue, suggesting their growing importance in NHL treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD20-based therapy of B cell lymphoma: state of the art. Kosmas, C., Stamatopoulos, K., Stavroyianni, N., et al.[2013]

TNB-486, a fully human bispecific antibody targeting CD19 and CD3, shows promise in treating B cell non-Hodgkin lymphoma (B-NHL) by inducing tumor cell lysis with minimal cytokine release, addressing safety concerns associated with existing therapies like blinatumomab and CAR-T.

In preclinical models, TNB-486 effectively cleared CD19+ tumor cells in immunocompromised mice and demonstrated pharmacokinetics similar to conventional antibodies, suggesting it could be a safer and more effective option for patients with B-NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL. Malik-Chaudhry, HK., Prabhakar, K., Ugamraj, HS., et al.[2022]

The bispecific antibody CD20-TCB is designed to enhance T-cell engagement, which could improve the effectiveness of immunotherapy in treating B-cell lymphoma, particularly in patients with relapsed or refractory non-Hodgkin lymphoma.

Preclinical models have shown promising activity for CD20-TCB, suggesting it may offer a new therapeutic option for patients who have not responded to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunity War: A Novel Therapy for Lymphoma Using T-cell Bispecific Antibodies. Prakash, A., Diefenbach, CS.[2019]

The tetravalent tandem diabody (tanDb) targeting CD19 and CD3 effectively eliminated malignant B cells from patients with B-cell chronic lymphocytic leukemia (B-CLL) in 19 out of 23 cases, demonstrating its potential as a powerful immunotherapy.

Unlike other antibody formats, the tanDb induced strong T cell activation and proliferation in the presence of CD19+ target cells, allowing for effective tumor cell lysis at very low concentrations, making it a promising candidate for treating B-cell leukemias and lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tetravalent bispecific CD19xCD3 recombinant antibody construct and CD28 costimulation on lysis of malignant B cells from patients with chronic lymphocytic leukemia by autologous T cells. Reusch, U., Le Gall, F., Hensel, M., et al.[2017]

The CD19/CD3 bi-specific antibody (BsAb) effectively targeted and bound to both CD19 and CD3-positive cells, demonstrating its potential for specific cancer therapy in non-Hodgkin's lymphoma (NHL).

In animal models, this BsAb not only stimulated T cell proliferation but also significantly inhibited tumor growth and prolonged survival in SCID mice, indicating its efficacy as a promising treatment option for NHL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fully human CD19/CD3 bi-specific antibody triggers potent and specific cytotoxicity by unstimulated T lymphocytes against non-Hodgkin's lymphoma. Zhou, Y., Gou, LT., Mu, B., et al.[2017]

The bispecific diabody (BsDb) targeting both CD19 and CD16 effectively recruits natural killer (NK) cells to attack non-Hodgkin's lymphoma cells, showing higher affinity for tumor cells compared to effector cells.

In a study with SCID mice, combining the CD19 x CD16 BsDb with another bispecific diabody and CD28 costimulation led to complete tumor elimination in 80% of cases, demonstrating a powerful synergistic effect in enhancing the anti-tumor response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic antitumor effect of bispecific CD19 x CD3 and CD19 x CD16 diabodies in a preclinical model of non-Hodgkin's lymphoma. Kipriyanov, SM., Cochlovius, B., Schäfer, HJ., et al.[2019]

In a phase I clinical trial involving 10 patients with relapsed/refractory non-Hodgkin lymphoma, the engineered T cells expressing a bispecific CAR targeting CD19 and CD20 demonstrated a high overall response rate of 90%, with 70% achieving complete remission.

The treatment was found to be safe, with no cases of neurotoxicity and only one instance of dose-limiting toxicity, indicating that CART19/20 T cells can provide effective therapy with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19/CD20 Bispecific Chimeric Antigen Receptor (CAR) in Naive/Memory T Cells for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma. Larson, SM., Walthers, CM., Ji, B., et al.[2023]

The CD3 x CD19 bispecific antibody (BsAb) effectively induced the killing of malignant B cells by resting T cells in preclinical tests, but required repeated doses and IL-2 to achieve significant tumor cell reduction in a 14-day assay.

In a small clinical study involving 4 patients, BsAb showed limited toxicity, primarily causing grade II fever and chills, while improving T cell activation; however, no significant clinical effects were observed in a patient with chronic lymphocytic leukemia, suggesting that further testing in patients with lower tumor burdens may be necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience with CD3 x CD19 bispecific antibodies in patients with B cell malignancies. De Gast, GC., Van Houten, AA., Haagen, IA., et al.[2018]

TNB-383B effectively induces the killing of plasma cells in bone marrow from patients with relapsed multiple myeloma, showing dose-dependent lysis starting at very low doses (0.001 μg).

The treatment leads to significant degranulation of cytotoxic T lymphocytes (CTLs) and modulates cytokine responses, with notable increases in IL-2/TNFα and IP10, indicating a robust immune response without significant T cell expansion or severe cytokine release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. Foureau, DM., Bhutani, M., Robinson, M., et al.[2023]

Triple negative breast cancer (TNBC) shows a higher potential for responding to immunotherapy due to its characteristics, such as increased tumor infiltrating lymphocytes and higher PD-L1 expression, making it a promising target for innovative treatments.

Current research is focused on exploring new immunotherapeutic strategies beyond immune checkpoint inhibitors, as these could provide safer and more effective options for treating TNBC, which has a poor prognosis and resists conventional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in triple negative breast cancer: beyond checkpoint inhibitors. Abdou, Y., Goudarzi, A., Yu, JX., et al.[2023]

Rituximab has been approved as an effective treatment for relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL), marking a significant advancement in therapy options for this disease.

Ibritumomab (Zevalin), a radioimmunotherapy targeting the CD20 antigen, has shown promising overall response rates of 64% and 67% in completed Phase I/II trials for various NHL types, with further trials currently ongoing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radioimmunotherapy of relapsed non-Hodgkin's lymphoma with zevalin, a 90Y-labeled anti-CD20 monoclonal antibody. Wiseman, GA., White, CA., Witzig, TE., et al.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8023237/

TNB-486 induces potent tumor cell cytotoxicity coupled with ... This study describes TNB-486, a novel fully human CD19xCD3 bispecific antibody designed for the treatment of B-NHL. TNB-486 engages CD19 and CD3, leading to ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04594642

A Study of AZD0486 in Subjects With B-Cell Non-Hodgkin ... This phase 1 study will investigate the safety, tolerability, pharmacokinetic, pharmacodynamic, and clinical activity of AZD0486, a CD19 x CD3 T-cell engaging ...

3. db.antibodysociety.org db.antibodysociety.org/db0/347/

AZD0486, TNB-486 Clinical Bispecific TNB-486 is a fully human bispecific antibody that binds CD19 with one arm and incorporates a unique anti-CD3 on the other. In preclinical studies, TNB-486 ...

4. tandfonline.com tandfonline.com/doi/abs/10.1080/19420862.2021.1890411

TNB-486 induces potent tumor cell cytotoxicity coupled ... In vivo, TNB-486 clears CD19+ tumor cells in immunocompromised mice in the presence of human peripheral blood mononuclear cells in multiple models. Additionally ...

5. froedtert.com froedtert.com/clinical-trials/multicenter-phase-1-open-label-dose-escalation-and-expansion-study-azd0486

A Multicenter, Phase 1, Open-Label, Dose-Escalation and ... The study drug, TNB-486, is a bispecific antibody. An antibody is a Y shaped protein used by your body's immune system to identify and destroy natural foreign ...

6. researchgate.net researchgate.net/publication/392304017_Safety_and_efficacy_of_AZD0486_a_CD19xCD3_T-cell_engager_in_relapsed_or_refractory_diffuse_large_B-cell_lymphoma

Safety and efficacy of AZD0486, a CD19xCD3 T-cell ... AZD0486, a novel IgG4 fully human CD19xCD3 bispecific T-cell engager, showed promising safety and efficacy in patients (pts) with heavily ...