AZD5492 for B-Cell Lymphoma

(TITANium Trial)

Recruiting at 30 trial locations

Overseen By AstraZeneca Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: AstraZeneca

Disqualifiers: CNS involvement, Burkitt's lymphoma, 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

174 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new treatment, AZD5492, to determine its safety and effectiveness for people with certain types of B-cell lymphoma, a kind of blood cancer. It targets those whose cancer has returned or not responded after at least two other treatments. The trial tests AZD5492 alone to target a protein called CD20, found on B-cells. Individuals with B-cell neoplasms, such as large B-cell lymphoma or chronic lymphocytic leukemia, whose disease has returned or worsened, may be suitable candidates. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I need to stop my current medications for the trial?

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 AZD5492 is likely to be safe for humans?

Research shows that AZD5492, a new treatment for B-cell lymphoma, appears promising in terms of safety. Previous studies suggest that this treatment, a special type of antibody targeting CD20, might be less toxic than other treatments, potentially causing less harm to the body.

Although detailed information remains limited, this trial is in the early stages, meaning researchers are closely monitoring for any side effects. Early studies of AZD5492 indicate it is well-tolerated, with a focus on ensuring its safety for use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

AZD5492 is unique because it targets B-cell lymphoma in a novel way. Unlike standard therapies, which often use chemotherapy or monoclonal antibodies, AZD5492 works by directly interfering with specific pathways critical to the survival of cancerous B-cells. This targeted approach may lead to fewer side effects and improved effectiveness for patients who have relapsed or are not responding to current treatments. Researchers are excited about AZD5492's potential to offer a new hope for those with limited options.

What evidence suggests that AZD5492 might be an effective treatment for B-Cell Lymphoma?

Research has shown that AZD5492, administered as monotherapy in this trial, could be a promising new treatment for certain types of B-cell lymphomas that have recurred or are resistant to other treatments. This experimental drug helps the immune system identify and destroy cancer cells. Early studies suggest that AZD5492 might cause fewer side effects, potentially making it safer than other treatments. Although still under investigation, its mechanism of targeting CD20—a protein often found on these cancer cells—appears promising for treating B-cell cancers. Similar treatments have already succeeded in treating various B-cell lymphomas. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for individuals with B-Cell Malignancies that have not responded to or have returned after previous treatments. Specific eligibility criteria are not provided, but typically participants must meet certain health standards and may be required to have a particular stage or type of disease.

Inclusion Criteria

I can do most of my daily activities on my own.

My condition worsened after two previous treatments.

My cancer is a type of B-cell lymphoma or leukemia.

Exclusion Criteria

I have side effects from cancer treatment that are moderate or worse, with some exceptions.

I haven't had a stem cell transplant or cell therapy in the last 3 to 6 months.

My lymphoma affects my brain or spinal cord.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies

Up to 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

What Are the Treatments Tested in This Trial?

Interventions

• AZD5492

Trial Overview The study is testing AZD5492, an experimental T cell-engaging antibody targeting CD20. It's in early stages (Phase I/II) to see if it's safe, tolerable, and effective for treating Relapsed or Refractory B-Cell Malignancies.

How Is the Trial Designed?

Group I: Module 1: AZD5492 Monotherapy Experimental Treatment 1 Intervention

AZD5492 monotherapy for Relapsed or Refractory B-Cell Malignancies.

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

In a study of 53 patients with relapsed/refractory marginal zone lymphoma (MZL) and follicular lymphoma (FL), the selective Bruton's tyrosine kinase inhibitor zanubrutinib showed an overall response rate of 80% for MZL and 36.4% for FL, indicating significant efficacy in these difficult-to-treat cancers.

Zanubrutinib was generally well tolerated, with most adverse events being mild (≤ grade 2), and no reports of atrial fibrillation/flutter, suggesting a favorable safety profile for patients undergoing treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Phillips, T., Chan, H., Tam, CS., et al.[2022]

In the phase III ALPINE trial, zanubrutinib, a second-generation BTK inhibitor, demonstrated superior efficacy compared to ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma.

Zanubrutinib not only showed a better safety profile but also significantly improved progression-free survival for patients, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BTK Inhibitor Options Expand for CLL/SLL. [2023]

In a study involving 18 patients with marginal zone lymphoma (MZL) treated with zanubrutinib, mutations in genes related to the NF-κB, NOTCH, and B-cell receptor pathways were found in 89% of the samples, indicating these mutations may play a significant role in the disease's response to treatment.

Specific mutations, such as MYD88 and TNFAIP3, were associated with improved progression-free survival (PFS), while KMT2D mutations were linked to worse PFS, highlighting the importance of genetic profiling in predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular associations of response to the new-generation BTK inhibitor zanubrutinib in marginal zone lymphoma. Tatarczuch, M., Waltham, M., Shortt, J., et al.[2023]

Zanubrutinib, a selective Bruton tyrosine kinase inhibitor, showed a high overall response rate of 94.5% in treatment-naïve patients with chronic lymphocytic leukemia or small lymphocytic lymphoma carrying the del(17p) mutation, indicating its efficacy in a challenging patient population.

The treatment was well tolerated, with an estimated 18-month progression-free survival rate of 88.6% and an overall survival rate of 95.1%, although some patients experienced adverse events, including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for patients with treatment naïve chronic lymphocytic leukemia and 17p deletion. Tam, CS., Robak, T., Ghia, P., et al.[2021]

In a phase 2 study involving 41 patients with relapsed or refractory non-GCB DLBCL, zanubrutinib showed a modest overall response rate of 29.3% and a complete response rate of 17.1%, indicating some effectiveness in this challenging subtype of lymphoma.

The safety profile of zanubrutinib was consistent with previous studies, with 48.8% of patients experiencing grade ≥ 3 adverse events, but no major hemorrhage or atrial fibrillation was reported, suggesting it may be a relatively safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib monotherapy for relapsed or refractory non-germinal center diffuse large B-cell lymphoma. Yang, H., Xiang, B., Song, Y., et al.[2022]

Zanubrutinib, a selective BTK inhibitor, was well-tolerated in a phase 1 study with 144 patients, showing no dose-limiting toxicities and achieving over 95% BTK occupancy in blood cells at all tested doses.

In patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), zanubrutinib demonstrated a remarkable overall response rate of 96.2% and a 100% estimated progression-free survival at 12 months, indicating strong efficacy with low major toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the selective BTK inhibitor zanubrutinib in B-cell malignancies and safety and efficacy evaluation in CLL. Tam, CS., Trotman, J., Opat, S., et al.[2021]

Zanubrutinib has been approved for treating various lymphoproliferative disorders, providing a significant option for patients who have not responded to standard therapies.

A panel of experts identified unmet clinical needs in the use of zanubrutinib for specific lymphomas, such as Waldenström macroglobulinemia, and made recommendations for future studies to optimize its use, especially for less experienced healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unmet clinical needs in the use of zanubrutinib in malignant lymphomas (Waldenström macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma): A consensus-based position paper from an ad hoc expert panel. Zinzani, PL., Mauro, FR., Tedeschi, A., et al.[2023]

A clinical trial combining R-CHOP with the BTK inhibitor zanubrutinib (ZR-CHOP) showed a high complete response rate in newly diagnosed double-expressor diffuse large B-cell lymphoma (DEL), although some patients, including one with ATM and CD58 mutations, experienced disease progression.

In vitro drug sensitivity testing identified that the patient with mutations responded well to a combination of bortezomib, thalidomide, and dexamethasone (VTD), leading to a complete response after subsequent treatment with VTD plus gemcitabine, demonstrating the potential of personalized therapy based on drug sensitivity profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Successful management of a refractory double-expressor diffuse large B-cell lymphoma patient under the guidance of in vitro high-throughput drug sensitivity test. Xing, L., Wang, H., Liu, D., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06542250

NCT06542250 | A Study to Evaluate Safety, PK, PD and ... A Study to Evaluate Safety, PK, PD and Efficacy of AZD5492, a T Cell-engaging Antibody Targeting CD20 in Subjects With R/​R B-Cell Malignancies. (TITANium).

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS7091

TITANium: An open-label, global multicenter phase 1/2 ... TITANium is a global Phase 1/2 multicenter dose escalation (Part A) and expansion (Part B) study (NCT06542250) of AZD5492 in pts with r/r B-cell malignancies.

3. astrazenecaclinicaltrials.com astrazenecaclinicaltrials.com/study/D9960C00001

A Study to Evaluate Safety, PK, PD and Efficacy of ... This is a Phase I/II study designed to evaluate if experimental T cell engaging antibody targeting CD20 AZD5492 is safe, tolerable and efficacious

4. rarediseaseadvisor.com rarediseaseadvisor.com/news/novel-trispecific-tce-reduce-toxicity-improve-safety-dlbcl/

Tri-Specific TCE May Reduce Toxicity, Improve Safety in ... AZD5492, a novel tri-specific T-cell engager, may reduce toxicity and improve safety in diffuse large B-cell lymphoma (DLBCL).

5. withpower.com withpower.com/trial/phase-2-neoplasms-7-2024-8564c

AZD5492 for B-Cell Lymphoma (TITANium Trial) The drug zanubrutinib, a similar BTK inhibitor, has shown effectiveness in treating various B-cell lymphomas, including marginal zone lymphoma and follicular ...

6. clinicaltrials.eu clinicaltrials.eu/trial/study-on-the-safety-and-effectiveness-of-azd5492-alone-or-with-other-treatments-for-adults-with-relapsed-or-refractory-b-cell-blood-cancers/

Study on the Safety and Effectiveness of AZD5492 Alone or ... This clinical trial investigates the safety and effectiveness of AZD5492, a T cell-engaging antibody, in treating adults with relapsed or refractory B-cell ...