AZD0486 for B-Cell Lymphoma

(SOUNDTRACK-B Trial)

Recruiting at 71 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants

Disqualifiers: CLL, CNS involvement, major cardiac, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This is a Phase 2 global, multi-center, open-label study to assess the efficacy, safety and tolerability of AZD0486 monotherapy in adult participants with relapsed/refractory B-cell non-Hodgkin lymphoma (NHL) who have received at least two prior lines of therapies. The study has 2 Modules: Module 1 for FL and Module 2 for DLBCL.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, it mentions that participants should not have had certain therapies like T-cell engager therapy or CAR T-cell therapy within specific time frames before starting the trial.

What data supports the effectiveness of the treatment AZD0486 for B-Cell Lymphoma?

Research shows that TNB-486, a similar treatment targeting CD19 and CD3, effectively kills tumor cells in B-cell non-Hodgkin lymphoma with minimal side effects in preclinical models. This suggests that AZD0486, which also targets CD19 and CD3, might be effective for B-cell lymphoma. ^{1 2 3 4 5}

What safety data exists for AZD0486 (TNB-486) in humans?

TNB-486, a treatment for B-cell lymphoma, has shown promising safety data in preclinical models, with minimal cytokine release (a type of immune response) compared to other treatments. This suggests it may have fewer side effects related to immune system overactivation, which is a common issue with similar therapies. ^{1 3 6 7 8}

How is the drug AZD0486 different from other treatments for B-cell lymphoma?

AZD0486 is unique because it is a fully human bispecific antibody that targets both CD19 on B cells and CD3 on T cells, inducing tumor cell destruction with minimal cytokine release, which reduces the risk of severe side effects compared to other treatments like CAR-T therapies. ^{1 2 3 9 10}

Eligibility Criteria

This trial is for adults with B-cell non-Hodgkin lymphoma (NHL) who have tried at least two other treatments without success. It's specifically aimed at those with certain types of NHL, like Follicular Lymphoma and Diffuse Large B-Cell Lymphoma.

Inclusion Criteria

I can do most activities by myself.

My blood counts meet the required levels for treatment.

My kidneys are functioning well, with a creatinine clearance rate of 45 mL/min or higher.

Exclusion Criteria

I have been diagnosed with CLL, Burkitt lymphoma, or Richter's transformation.

My brain or spinal cord is affected by non-Hodgkin lymphoma.

My B-cell non-Hodgkin lymphoma is showing up in my blood.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD0486 monotherapy administered as an intravenous infusion

12-24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 5 years

Treatment Details

Interventions

• AZD0486 (Monoclonal Antibodies)

Trial Overview The study is testing AZD0486 as a single treatment option. Participants are divided into two groups based on their type of NHL: one group for Follicular Lymphoma (Module 1) and another for Diffuse Large B-Cell Lymphoma (Module 2).

Participant Groups

Group I: Module 2: AZD0486 Monotherapy in Participants with Relapsed or Refractory DLBCL Experimental Treatment 1 Intervention

In Module 2, the efficacy and safety of AZD0486 at the RP2D will be evaluated in R/R DLBCL. AZD0486 will be administered as intravenous infusion.

Group II: Module 1: AZD0486 Monotherapy in Participants with Relapsed or Refractory Follicular Lymphoma Experimental Treatment 1 Intervention

In Module 1, the efficacy and safety of AZD0486 at the RP2D will be evaluated in R/R FL. AZD0486 will be administered as intravenous infusion.

Who Is Running the Clinical Trial?

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

Findings from Research

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 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]

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 study successfully developed two anti-CD19 monoclonal antibodies, C19Mab-1 and C19Mab-3, using different methods, which can be used for detecting CD19 in various assays related to B cell malignancies.

These antibodies can aid in the pathological analysis of CD19, which is crucial for the treatment of patients with CD19-positive relapsed or refractory B cell cancers, enhancing the effectiveness of therapies like Blinatumomab and tisagenlecleucel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Novel Mouse Monoclonal Antibodies Against Human CD19. Yamada, S., Kaneko, MK., Sayama, Y., et al.[2021]

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]

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]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

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]

CD6 is highly expressed in nearly all examined T cell lymphoma (TCL) patient samples, indicating it could be a promising new target for therapy in this aggressive cancer.

The CD6-targeted antibody-drug conjugate (CD6-ADC) effectively killed TCL cells in laboratory tests and significantly reduced tumor growth in preclinical mouse models, suggesting its potential as a new treatment option for patients with TCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD6-targeted antibody-drug conjugate as a new therapeutic agent for T cell lymphoma. Parameswaran, N., Luo, L., Zhang, L., et al.[2023]

References

1. United States 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. [2017]

2. United States pubmed.ncbi.nlm.nih.gov

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

3. United States pubmed.ncbi.nlm.nih.gov

TNB-486 induces potent tumor cell cytotoxicity coupled with low cytokine release in preclinical models of B-NHL. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

G protein-coupled receptor 183 mediates the sensitization of Burkitt lymphoma tumors to CD47 immune checkpoint blockade by anti-CD20/PI3Kδi dual therapy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Development of Novel Mouse Monoclonal Antibodies Against Human CD19. [2021]

6. United States 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Ex vivo efficacy of BCMA-bispecific antibody TNB-383B in relapsed/refractory multiple myeloma. [2023]

8. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Anti-CD20-based therapy of B cell lymphoma: state of the art. [2013]

10. England pubmed.ncbi.nlm.nih.gov

CD6-targeted antibody-drug conjugate as a new therapeutic agent for T cell lymphoma. [2023]