Tegavivint for Large B-Cell Lymphoma

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Lapo Alinari

Must not be taking: Antiretrovirals

Disqualifiers: CNS lymphoma, Hepatitis B, Hepatitis C, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a new drug, tegavivint, to determine its safety and effectiveness for individuals with certain types of large B-cell lymphoma that have recurred or resisted other treatments. Tegavivint blocks enzymes essential for cancer cell growth, potentially helping to control the disease. This study suits those who have undergone at least two previous lymphoma treatments and are ineligible for or have declined certain advanced therapies. Participants will receive tegavivint through an IV and undergo several scans and blood tests to monitor its effects. As a Phase 1 trial, this research aims to understand how tegavivint 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 to join the trial?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on HIV medications or other drugs that interact with tegavivint, you may not be eligible to participate.

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

Research has shown that tegavivint is safe and tolerable in patients with other tumors, such as desmoid tumors. Patients generally handled the treatment well, with most side effects being mild. In studies involving patients with advanced liver cancer, certain doses of tegavivint also appeared safe, with mostly mild side effects reported.

As this is a Phase 1 trial, the main goal is to assess the safety of tegavivint in people with relapsed or refractory large B-cell lymphoma. Earlier studies in different conditions suggest it might be well-tolerated, but this trial will help confirm its safety for large B-cell lymphoma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tegavivint is unique because it targets the TBL1 protein, which plays a critical role in the growth of large B-cell lymphoma. Unlike standard treatments like chemotherapy, which broadly attack fast-growing cells and can lead to significant side effects, Tegavivint offers a more targeted approach, potentially reducing collateral damage to healthy cells. Researchers are excited about its ability to specifically disrupt cancer cell signaling pathways, which might offer a more effective and less toxic treatment option for patients.

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

Research has shown that tegavivint, the investigational treatment in this trial, might stop tumors from growing by blocking signals cancer cells need. Early lab studies found that tegavivint can shrink tumors with a protein called beta-catenin, which aids cell growth. This is crucial because, in certain large B-cell lymphomas, especially those that recur or resist treatment, standard therapies often fail. By targeting the beta-catenin pathway, tegavivint might offer a new approach to managing these challenging cancers. These early results are promising, but ongoing studies must confirm its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Lapo Alinari, MD, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

Adults with relapsed or refractory large B-cell lymphoma who have tried at least two treatments and can't or won't get stem cell transplant or CAR T-cell therapy. They must have measurable disease, adequate organ function, agree to use contraception, and not be pregnant. Excluded are those with certain infections, recent major surgery, other active cancers (with exceptions), uncontrolled illnesses, known allergies to similar drugs, HIV on specific treatments, active CNS lymphoma.

Inclusion Criteria

Patients must be willing and able to understand and give written informed consent and comply with all study related procedures

Platelet count > 75,000/mcL

Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x institutional ULN

Exclusion Criteria

I do not have serious heart disease or abnormal heart rhythm issues.

I have an active tuberculosis infection.

Patients with abnormal serum chemistry values other than the specific limits detailed above, that in the opinion of the investigator is considered to be clinically significant, should be discussed with the medical monitor before being enrolled in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive tegavivint intravenously (IV) and undergo CT and/or PET scans and blood sample collection throughout the trial

14 weeks

Multiple visits for IV administration and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Tegavivint

Trial Overview

The trial is testing the safety and optimal dosage of a drug called tegavivint for patients whose large B-cell lymphomas have returned after treatment or haven’t responded to previous therapies. The study involves collecting biospecimens and using imaging tests like CT scans and PET scans to monitor the effects.

How Is the Trial Designed?

Group I: Treatment (Tegavivint) Experimental Treatment 6 Interventions

Patients receive tegavivint IV over 4 hours on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and/or PET and undergo blood sample collection throughout the trial. Patients may also undergo bone marrow biopsy and aspirate during screening and on the trial.

Who Is Running the Clinical Trial?

Lapo Alinari

Lead Sponsor

Trials

1

Recruited

20+

Published Research Related to This Trial

Recent advancements in therapies for diffuse large B-cell lymphoma (DLBCL) include new agents like polatuzumab combined with bendamustine and rituximab, which are non-cytotoxic and aim to improve patient outcomes.

The approval of CAR-T cell therapies and ongoing development of bispecific antibodies and antibody drug conjugates suggest a promising future for targeted combination therapies in treating B-cell malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diffuse large B-cell lymphoma: new targets and novel therapies. Cheson, BD., Nowakowski, G., Salles, G.[2022]

Polatuzumab vedotin is an antibody-drug conjugate that has shown significant clinical activity and an acceptable safety profile in treating relapsed or refractory diffuse large B-cell lymphoma (DLBCL), particularly when combined with anti-CD20 monoclonal antibodies and chemotherapy.

The recent POLARIX trial suggests that polatuzumab may also be effective in frontline treatment for DLBCL, potentially changing its role in managing patients who have not responded to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin in relapsed / refractory aggressive B-cell lymphoma. Varma, G., Wang, J., Diefenbach, C.[2022]

In a phase 3 trial involving 879 patients with untreated intermediate-risk or high-risk diffuse large B-cell lymphoma (DLBCL), the modified regimen pola-R-CHP (which replaces vincristine with polatuzumab vedotin) showed a significantly higher progression-free survival rate at 2 years (76.7%) compared to the standard R-CHOP regimen (70.2%).

The overall survival rates at 2 years were similar between the pola-R-CHP and R-CHOP groups (88.7% vs. 88.6%), indicating that while pola-R-CHP may reduce the risk of disease progression, it does not significantly improve overall survival compared to the standard treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. Tilly, H., Morschhauser, F., Sehn, LH., et al.[2022]

Polatuzumab vedotin (PoV) combined with chemotherapy showed a 52.5% overall response rate in 40 patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), indicating it is an effective treatment option.

The median overall survival for patients receiving PoV was 8.5 months, but those who underwent subsequent hematopoietic stem cell transplantation had a significantly improved survival of 24 months, highlighting the importance of this treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab vedotin-based salvage immunochemotherapy as third-line or beyond treatment for patients with diffuse large B-cell lymphoma: a real-world experience. Wang, YW., Tsai, XC., Hou, HA., et al.[2022]

In a study of patients with transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL), the combination of polatuzumab vedotin with bendamustine and rituximab (pola-BR) resulted in a significantly higher complete response (CR) rate of 40% compared to 17.5% with bendamustine and rituximab alone, indicating improved efficacy.

Patients receiving pola-BR also experienced longer progression-free survival (9.5 months vs. 3.7 months) and overall survival (12.4 months vs. 4.7 months), although there were higher rates of certain side effects like neutropenia and peripheral neuropathy, which were mostly manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma. Sehn, LH., Herrera, AF., Flowers, CR., et al.[2021]

Citations

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Tegavivint for Treating Patients with Relapsed or ...

This phase I trial tests the safety, side effects, and best dose of tegavivint in treating patients with large b-cell lymphomas that has come back ...

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asco.org/abstracts-presentations/ABSTRACT455986

A phase 1/2 study of the TBL1 inhibitor, tegavivint (BC2059 ...

Tegavivint treatment of established β-cateninexon3 activated tumors resulted in reduced tumor growth and burden. Based on these promising preclinical results, ...

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clinicaltrials.gov/study/NCT04851119

NCT04851119 | Tegavivint for the Treatment of Recurrent ...

Tegavivint interferes with the binding of beta-catenin to TBL1, which may help stop the growth of tumor cells by blocking the signals passed from one molecule ...

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prnewswire.com

prnewswire.com/news-releases/iterion-therapeutics-announces-the-initiation-of-a-phase-1-clinical-trial-for-tegavivint-in-patients-with-c-myc-overexpressing-relapsed-or-refractory-large-b-cell-lymphomas-301825538.html

Iterion Therapeutics Announces the Initiation of a Phase 1 ...

Patients with c-Myc-overexpressing DLBCL are less likely to respond to currently available therapies, with an overall survival (OS) rate of 30% ...

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tegavivint (BC2059) / Iterion Therap, Apollomics

IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma ...

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Tegavivint May Be Safe and Tolerable for Treatment ...

In patients with desmoid tumors, tegavivant has demonstrated early safety and tolerability.

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Tegavivint Demonstrates Preliminary Antitumor Activity, ...

Administration of tegavivint at doses of up to 6.5 mg/kg weekly demonstrated early signs of efficacy and safety, with primarily low-grade ...