AZD0486 for B-Cell Lymphoma

(SOUNDTRACK-B Trial)

Recruiting at 91 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AstraZeneca

Must not be taking: Immunosuppressants

Disqualifiers: CLL, CNS involvement, major cardiac, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12-24 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Surovatamig (AZD0486) for individuals with B-cell non-Hodgkin lymphoma that has recurred or resisted other treatments. The trial aims to evaluate the treatment's effectiveness and safety. It consists of two parts: one for follicular lymphoma and another for large B-cell lymphoma. Participants must have undergone at least two previous treatments and still exhibit symptoms to qualify. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group.

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.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that AZD0486, also known as Surovatamig, was safe in earlier studies. In past trials, patients with heavily treated follicular lymphoma tolerated it well. Some side effects occurred, but they were generally manageable.

AZD0486 is a medicine that helps the immune system attack cancer cells. Lab studies have shown it effectively kills cancer cells while causing minimal inflammation.

This trial is in Phase 2, indicating that AZD0486 has already passed initial safety tests in humans. This suggests it is reasonably safe for more extensive testing. Prospective participants might find this information reassuring regarding the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for B-cell lymphoma?

Researchers are excited about AZD0486, also known as surovatamig, because it offers a fresh approach to treating B-cell lymphomas like follicular lymphoma and large B-cell lymphoma. Unlike standard treatments such as chemotherapy and Rituximab, surovatamig targets the disease with a unique mechanism by using a novel active ingredient that is administered through intravenous infusion. This could potentially improve effectiveness and safety for patients who have relapsed or are refractory to existing therapies. Additionally, its targeted action may result in fewer side effects, offering a more tolerable treatment option for those with these challenging conditions.

What evidence suggests that AZD0486 might be an effective treatment for B-cell lymphoma?

Research shows that AZD0486, also known as surovatamig, could effectively treat relapsed or hard-to-treat B-cell non-Hodgkin lymphoma (NHL). Previous studies found that this treatment worked well and was safe for patients with this condition. In this trial, participants with follicular lymphoma (FL) will receive surovatamig monotherapy, which previous studies have shown to be both safe and effective, even for patients who had many prior treatments. Participants with diffuse large B-cell lymphoma (LBCL) will also receive surovatamig monotherapy, where earlier studies showed high rates of complete response, especially in those who hadn't tried CAR-T therapy before. These findings suggest that AZD0486 might be a promising option for people whose lymphoma hasn't improved with other treatments. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AZD0486

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).

How Is the Trial Designed?

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

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

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

In Module 1, the efficacy and safety of surovatamig at the RP2D will be evaluated in R/R FL. Surovatamig 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

Published Research Related to This Trial

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]

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]

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 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]

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-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]

TG-1801, a bispecific antibody targeting CD47 on CD19+ B-cells, enhances the effectiveness of anti-CD20 therapies by promoting antibody-dependent cell death (ADCC) and phagocytosis (ADCP), leading to significant antitumor effects in B-cell non-Hodgkin lymphoma (B-NHL) models.

The combination of TG-1801 with ublituximab and the PI3Kδ inhibitor umbralisib (U2 regimen) showed remarkable and durable antitumor effects, with GPR183 identified as a key factor in the efficacy of this triplet therapy, suggesting its potential as a target for further clinical evaluation.

NCBI (Pubmed)

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. Ribeiro, ML., Profitós-Pelejà, N., Santos, JC., et al.[2023]

Citations

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

TNB-486 induces potent tumor cell cytotoxicity coupled with ... Data in Table 3 shows that TNB-486 induced the autologous T cell killing of >10% B cells in 6 of 8 samples tested. Table 3. TNB-486 mediates lysis of tumor ...

2. researchgate.net researchgate.net/publication/386477411_Evaluation_of_AZD0486_a_Novel_CD19xCD3_T-Cell_Engager_in_RelapsedRefractory_Diffuse_Large_B-Cell_Lymphoma_in_an_Ongoing_First-in-Human_Phase_1_Study_High_Complete_Responses_Seen_in_CAR-T-Naive_and_CAR

Evaluation of AZD0486, a Novel CD19xCD3 T-Cell ... AZD0486 was active and well tolerated in patients (pts) with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL), including those with ...

3. 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 ...

4. asco.org asco.org/abstracts-presentations/ABSTRACT492318

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 pretreated follicular ...

5. ascopubs.org ascopubs.org/doi/10.1200/EDBK-25-473302

Chimeric Antigen Receptor T-Cell Therapy and Bispecific ... This review aims to provide an overview of cellular therapy and BsAbs use in large B-cell lymphoma (LBCL), follicular lymphoma (FL), and mantle cell lymphoma ( ...

6. db.antibodysociety.org db.antibodysociety.org/db0/347/

AZD0486, TNB-486 Clinical Bispecific In preclinical studies, TNB-486 induced T-cell dependent killing of CD19-positive B-cell leukemia and lymphoma cells while inducing minimal cytokine secretion, ...

7. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D7404C00001

Surovatamig (AZD0486) as Monotherapy in Participants ... This is a Phase 2 global, multi-center, open-label study to assess the efficacy, safety and tolerability of Surovatamig (AZD0486) monotherapy in adult ...